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Abramson Cancer Center
NCI CANCERLIT® Search: Therapy of Ovarian Cancer - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- IDM 1. IDM-1, MAK/IDM-1.
- Antagonistic effect of the combination gemcitabine/topotecan in ovarian cancer cells.
- [Combined treatment and prognostic analysis of advanced epithelial ovarian carcinoma]
- [Clinical significance of secondary cytoreductive surgery for recurrent advanced ovarian cancer]
- [Ovarian cancer]
- The cellular pharmacology of oxaliplatin resistance.
- Ovarian cancer.
- Prognostic factors in salvage therapy of ovarian cancer.
- Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients [seecomments]
- Utility of the SEER-Medicare data to identify chemotherapy use.
- [Latest information in the diagnoses of ovarian carcinoma]
- [Treatment of malignant ovarian germ cell tumor and sex cord tumors]
- [Ovarian cancer]
- Phase I and pharmacological study of single paclitaxel administered weekly for heavily pre-treated patients with epithelial ovarian cancer.
- Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian cancer: expression of coxsackie-adenovirus receptor and integrins
- Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors.
- Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer.
- Local radiation therapy for localized relapsed or refractory ovarian cancer patients with or without symptoms after chemotherapy.
- [Antisense oligodeoxynucleotides of human telomerse catalytic sub-unit inhibits telomerase activity and proliferation in SKOV3 and COC1]
- [Effects of RelA antisense oligonucleotide on apoptosis of ovarian cancer cells COC1]
- Cell viability assay for drug testing in ovarian cancer: in vitro kill versus clinical response.
- Hematological toxicity of salvage treatment after high-dose chemotherapy and conventional chemotherapy of ovarian cancer.
- Treatment of micropapillary serous ovarian carcinoma (the aggressive variant of serous borderline tumors).
- Recurrent micropapillary serous ovarian carcinoma.
- Results of ovary tumor treatment with abdominally administered (198)Au evaluated on the basis of long term follow up.
- [Laparoscopic colostomy: experience in patients with ovarian or ano-rectal cancer, non-operable or with rectovaginal fistula]
- Patient-controlled thoracic epidural infusion with ropivacaine 0.375% provides comparable pain relief as bupivacaine 0.125% plus sufentanil
- The effect of residual mass size on response to chemotherapy after surgical cytoreduction for advanced ovarian cancer: long-term results.
- Clinical practice guidelines: loss of clinical freedom or a coming of age?
- [Study of mdr1 antisense oligodeoxynucleotides on reversal of multidrug resistance in ovarian carcinoma cell line SKOV3]
- [Surgical treatment of stage III-IV ovarian cancer]
- Part I: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis.
- Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease.
- Novel immunotherapeutic strategies in gynecologic oncology. Dendritic cell-based immunotherapy for ovarian cancer.
- Sequence-dependent synergism between the new generation platinum agent ZD0473 and paclitaxel in cisplatin-sensitive and -resistant human
- Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma.
- Quantification of the completeness of follow-up.
- Current treatment for ovarian cancer.
- Tamoxifen therapy for ovarian cancer in the adjuvant and advanced settings: systematic review of the literature and implications for
- The immunotherapy of patients with ovarian cancer.
- Age contrasts in clinical characteristics and pattern of care in patients with epithelial ovarian cancer.
- No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer.
- A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to
- Comparison of tolerance of combination carboplatin and paclitaxel chemotherapy by age in women with ovarian cancer.
- Does the interval from primary surgery to chemotherapy influence progression-free survival in ovarian cancer?
- The role of tamoxifen in the management of ovarian cancer.
Table of Contents
1
UI - 11881531
AU - Anonymous
TI -
IDM 1. IDM-1, MAK/IDM-1.
SO - Drugs R D 2002;3(1):50-1
2
UI - 11697814
AU - Distefano M; Ferlini C; De Vincenzo R; Gaggini C; Mancuso S; Scambia G
TI -
Antagonistic effect of the combination gemcitabine/topotecan in ovarian
cancer cells.
SO - Oncol Res 2000;12(9-10):355-9
AD - Department of Obstetrics and Gynecology, Catholic University of the
Sacred Heart, Rome, Italy.
The in vitro interaction between the new antimetabolite gemcitabine
(GEM) and topotecan (TPT) was analyzed in A2780 ovarian cancer cells.
The growth inhibitory effect was assessed after 3 days of drug exposure.
GEM and TPT obtained in vitro IC50 values of 2.1 +/- 0.9 and 33.7 +/-
10.2 nM, respectively. The interaction between GEM and TPT was evaluated
by exposing cancer cells at increasing doses of GEM (0.1, 1, and 10 nM)
and TPT (1, 10, 100, and 1000 nM). Analysis of data about the
interaction between GEM and TPT was performed by applying the isobole
method. An antagonistic effect was noticed when GEM was combined with
TPT in the tested concentration range. DNA analysis was also performed
and showed an augmentation of cells blocked in the G2/M phase during TPT
exposure, while an increase of blocked cells in the G0/1, phase was
observed after GEM treatment. This latter effect was predominant when
the two drugs were used in combination. We also investigated the effect
of sequential exposure to drugs, pretreating A2780 cells for 24 h with
TPT and then for 48 h with GEM, and, conversely, pretreating A2780 cells
with GEM for 24 h and thereafter with TPT for 48 h. Both these combined
sequential treatments showed an antagonist effect of the drugs'
combination. Long-term growth inhibition effect was established by
clonogenic assay performed after 10 days of culture after drug
treatment. Also these data confirmed the antagonistic effect between GEM
and TPT in A2780 ovarian cancer cells.
3
UI - 12133404
AU - Huang X; Cai S; Fan J; Li Z
TI -
[Combined treatment and prognostic analysis of advanced epithelial
ovarian carcinoma]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 May;37(5):291-3
AD - Department of Gynecology, Cancer Hospital, Fudan University, Shanghai
200032, China.
OBJECTIVE: To evaluate the effects of combined treatment for advanced
epithelial ovarian carcinoma and to analyze its prognostic factors.
METHODS: Fifty-three patients treated with a three-step combined
therapeutic regimen were defined as research arm. The procedures of the
three-step combined treatment were as follows: induction of tumor
remission, sequential chemotherapy and adjuvant immunotherapy. Three
hundred and eighteen patients with advanced epithelial ovarian carcinoma
treated with cytoreductive surgery and systemic chemotherapy were
retrospectively classified into control arm. RESULTS: The rates of
complete response and partial response in the research arm were
significantly differed from those in the control arm (90.6%, 5.7% Vs
70.1%, 5.3%, P < 0.01). The 1-, 2- and 3-year survival rates of the
research arm and control arm were 97.7%, 89.1%, 83.6% Vs 71.8%, 44.1%,
29.8%, respectively (P < 0.01). The 1-, 2- and 3-year tumor-free
survival rates of the research arm and control arm were 92.6%, 75.0%,
75.0% Vs 60.3%, 37.8%, 28.6%, respectively (P < 0.01). The 1- and 2-year
recurrent rates of the patients in research arm were much lower than
that in control arm (7.5%, 25.0% Vs 39.7%, 62.2%, P < 0.01). Age, stage,
ascites, differential degree, preoperative chemotherapy (intraperitoneal
and/or intravenous chemotherapy), postoperative intraperitoneal
chemotherapy and systemic chemotherapy were poor prognostic factors.
Initially treated in other hospital, bilateral tumors, large residuals
(diameter more than 1cm) and postoperative intraperitoneal chemotherapy
were poor tumor-free survival prognostic factors. CONCLUSION: Combined
therapy including remission induction, consolidation chemotherapy and
immunotherapy was able to enhance therapeutic efficacy, decrease the 1-
and 2-year recurrent rate and improve the survival of patients with
advanced epithelial ovarian carcinoma.
4
UI - 12015048
AU - Zang R; Zhang Z; Cai S
TI -
[Clinical significance of secondary cytoreductive surgery for recurrent
advanced ovarian cancer]
SO - Zhonghua Zhong Liu Za Zhi 2002 Mar;24(2):194-6
AD - Department of Gynecological Oncology, Cancer Hospital, Fudan University,
Shanghai 200032, China.
OBJECTIVE: To study the role of secondary cytoreductive surgery (SCR) in
patients with recurrent advanced epithelial ovarian cancer. METHODS:
From Jan. 1986 to Dec. 1997, 60 women with recurrent advanced epithelial
ovarian cancer treated with SCR were retrospectively reviewed. Survival
curves were computed using the Kaplan-Meier method with differences in
survival estimated by log-rank test. Independent prognostic factors were
identified by Cox's stepwise regression, and the affecting factors of
SCR evaluated by Logistic stepwise regression. RESULTS: Of the 60
patients, 23 (38.3%) were cytoreduced to small macroscopic residual ( 12 months and without refractory ascites.
5
UI - 12082861
AU - Bertelsen K; Knudsen JB
TI -
[Ovarian cancer]
SO - Ugeskr Laeger 2002 Jun 3;164(23):3056-9
AD - Onkologisk haematologisk afdeling R, Odense Universitetshospital,
DK-5000 Odense C.
6
UI - 12091073
AU - Mishima M; Samimi G; Kondo A; Lin X; Howell SB
TI -
The cellular pharmacology of oxaliplatin resistance.
SO - Eur J Cancer 2002 Jul;38(10):1405-12
AD - Department of Obstetrics and Gynecology, University of Tokyo, Japan.
Oxaliplatin is a third generation platinum compound that differs from
cisplatin and carboplatin in having a broader spectrum of antitumour
activity. Molecular studies suggest that oxaliplatin adducts are
recognised and processed differently than those produced by the earlier
generation Pt-containing drugs. We report here studies on the kinetics
of the development of oxaliplatin resistance, and the changes in the
cellular pharmacology of oxaliplatin that accompany the emergence of the
resistant phenotype in five parental human tumour cell lines and their
sub-lines selected for acquired oxaliplatin resistance in vitro. During
selection, resistance did not substantially increase until after at
least six cycles of oxaliplatin treatment. Oxaliplatin demonstrated
schedule-dependency with a 1-h exposure being substantially less
cytotoxic than a continuous exposure. Whole cell uptake was linear with
concentration, but uptake in the resistant cells averaged only 27+/-10
S.D.% of that in the sensitive cells. Pt accumulation in DNA was
markedly reduced in four of the five resistant cell lines, but this did
not correlate with either IC(50) or total cellular accumulation. Four of
the five resistant sub-lines also demonstrated increased tolerance to
adducts in DNA that ranged from 3.1 to 7.6-fold. We conclude that
development of acquired resistance to oxaliplatin is accompanied by
independent defects in both whole cell uptake and in adduct formation.
7
UI - 12184040
AU - Martin VR
TI -
Ovarian cancer.
SO - Semin Oncol Nurs 2002 Aug;18(3):174-83
AD - Ambulatory Care, Fox Chase Cancer Center, 7701 Burholme Ave,
Philadelphia, PA 19111, USA.
OBJECTIVES: To review the progress in the management of ovarian cancer
in the last decade and future directions. DATA SOURCES: Research
studies, review articles, and abstracts. CONCLUSIONS: There is an
increased understanding of ovarian cancer biology, the genetic basis for
hereditary ovarian cancer, staging and the role of cytoreductive
surgery, and more effective chemotherapy, resulting in an increase in
the percentage of patients who will live 5 years from the time of
diagnosis. IMPLICATIONS FOR NURSING PRACTICE: The nurse can play an
invaluable role as the options of treatment are considered and weighed
against quality-of-life considerations.
8
UI - 9402163
AU - Markman M
TI -
Prognostic factors in salvage therapy of ovarian cancer.
SO - Ann Oncol 1997 Oct;8(10):937-8
9
UI - 9402168
AU - Eisenhauer EA; Vermorken JB; van Glabbeke M
TI -
Predictors of response to subsequent chemotherapy in platinum pretreated
ovarian cancer: a multivariate analysis of 704 patients [seecomments]
SO - Ann Oncol 1997 Oct;8(10):963-8
AD - National Cancer Institute of Canada Clinical Trials Group, Queen's
University, Kingston.
BACKGROUND: The probability of response to chemotherapy following
platinum based treatment in ovarian cancer has usually been related to
the 'platinum-free interval'. However, in a recent European-Canadian
trial of paclitaxel, serous histology, tumor bulk, and hemoglobin, but
not treatment free interval, were predictors of response. To determine
if these observations were unique to this study (or this drug), data
from other active agents given as second- or third-line treatment in
ovarian cancer were obtained and analyzed. METHODS: In the first part of
the study, results of trials in 1185 platinum pretreated ovarian cancer
patients were obtained on six agents: paclitaxel, epirubicin, docetaxel,
carboplatin, irinotecan, and gemcitabine. Response results according to
histology, baseline hemoglobin, tumor size and time from last
chemotherapy were determined for each agent and the
Cochran-Mantel-Haenszel procedure was used to obtain an overall
assessment of significance for each factor. In the second part of the
study, individual data from 704 patients in four studies (three agents:
paclitaxel, docetaxel and epirubicin) were pooled for univariate and
multivariate analysis of factors predictive of response. RESULTS: In the
analysis of results of individual agents all factors examined were
significant predictors of response: serous histology (P = 0.001), tumor
size < or = 5 cm (P = 0.02), normal baseline hemoglobin (P = 0.003), and
> or = 6 mo since last treatment (P = 0.001). While these results were
interesting, they did not supply definitive answers regarding
independent response predictors. Therefore a multifactor analysis was
undertaken on the 704 patients for whom individual data were available.
Of the 11 factors examined in a univariate analysis, 10 met the criteria
for inclusion in a stepwise logistic regression. In the final model only
3 factors remained as significant independent predictors of response:
serous histology (P = 0.009), no. disease sites (P = 0.003), and tumor
size (P = 0.001). Time from last treatment, when evaluated as a
continuous variable, was not in the final model and was highly
correlated with tumor size (P = 0.0005). CONCLUSIONS: On the basis of
this analysis, we conclude that tumor burden (as assessed by size of the
largest lesion and number of disease sites) and histology are factors of
importance in response to subsequent chemotherapy in relapsed ovarian
cancer. Time from last treatment was correlated with tumor size in this
data set and its effect on response was dependent on whether it was
examined as a categorical or continuous variable, so we conclude it is
not the sole critical factor of biologic importance. We recommend
description of these factors in reports of phase II studies,
confirmation of these findings in other data sets and further
investigation of the mechanism of sensitivity of serous tumors.
10
UI - 12187169
AU - Warren JL; Harlan LC; Fahey A; Virnig BA; Freeman JL; Klabunde CN;
TI -
Cooper GS; Knopf KB
Utility of the SEER-Medicare data to identify chemotherapy use.
SO - Med Care 2002 Aug;40(8 Suppl):IV-55-61
AD - Applied Research Program, National Cancer Institute, Bethesda, Maryland
20892-7344, USA.joan_warren@nih.gov
BACKGROUND: Medicare claims include codes for chemotherapy
administration and specific drugs given, and researchers are
increasingly using these data to measure the use of chemotherapy.
However, the validity and completeness of these data as a source of
information has not been established. OBJECTIVES: This analysis is
intended to assess the utility of the Medicare claims to capture
chemotherapy use. METHODS: Persons with breast, colorectal, and ovarian
cancer were identified from the linked SEER-Medicare data. Their
Medicare claims were reviewed to determine if there were any bills for
chemotherapy, and if so, if there were claims for specific agents. This
information was compared with data on the first course of treatment
obtained from hospitals and treating physicians by the SEER registries
through an NCI-supported Patterns of Care Studies (POC). Agreement was
measured using kappa statistics. The sensitivity of the Medicare claims
to capture chemotherapy, as reported from the POC data, was also
measured. An additional comparison assessed the agreement between the
two data sources concerning which specific drugs had been given.
RESULTS: For all of the cancers, there was a high level of agreement
between the Medicare claims and the POC data regarding whether or not
the patient had received chemotherapy (kappa >or=0.73). The sensitivity
of the Medicare data to determine if a person had received chemotherapy
was high (>or=88%). In cases where the Medicare claim included a code
for a specific drug, there high agreement between Medicare and POC about
the specific drug given in breast and colorectal cancers, although the
agreement was lower for ovarian cancers. The sensitivity of the Medicare
claims to identify specific agents varies by cancer type. CONCLUSIONS:
The Medicare claims can be used to identify which persons are receiving
chemotherapy. The utility of Medicare data to measure treatment with
specific agents varies by cancer type and specific agent. For some
cancers, it is possible to use these claims to assess use of specific
drugs, while for other drugs the data are limited.
11
UI - 12214460
AU - Isonishi S
TI -
[Latest information in the diagnoses of ovarian carcinoma]
SO - Gan To Kagaku Ryoho 2002 Aug;29(8):1351-7
AD - Dept. of Obstetrics and Gynecology, Jikei University School of Medicine.
Despite improvements in median and overall survival from a combination
of improved operation techniques and chemotherapy with
platinum-compounds and paclitaxel, long-term survival rates for patients
with epithelial ovarian carcinoma remain disappointing, and ongoing
efforts are aimed at developing more effective primary therapies. In
early ovarian carcinoma, conservative management is used to denote
surgery that preserves reproductive potential without compromising
curability. With some exceptions, such a strategy may be applicable for
women younger than 40, who wish to bear children. A major dilemma facing
gynecologic oncologists is to determine whether the accurate staging
laparotomy is needed for apparent low-risk stage I ovarian carcinoma and
how many cycles of chemotherapy will be needed for high-risk stage I
ovarian carcinoma. In advanced ovarian carcinoma, main objectives of
salvage therapy include: a improvement in quality of life and symptoms;
b. tumor load reduction and survival advantage; c. evaluation of
potentially active new drugs to be included in first-line treatment. We
need to evaluate the potential benefit on survival of systematic pelvic
and para-aortic lymphadenectomy during primary or secondary
cytoreductive surgery in patients with advanced ovarian carcinoma.
Paclitaxel/cisplatin is considered to be the international standard
treatment based on the data of GOG 111 trial showing that
paclitaxel/cisplatin has provided a survival benefit better than that of
cyclophosphamide/cisplatin. This choice of standard therapy might,
however, be questioned based on the results of the largest randomised
study, ICON3. There were no statistically significant differences in
progression-free or overall survival among paclitaxel/carboplatin and
carboplatin only or a platinum combination
(cyclophosphamide/doxorubicin/cisplatin). The best selection for
adjuvant chemotherapy is still controversial and a large number of
studies are now ongoing.
12
UI - 12214461
AU - Sugiyama T; Ohta S; Tomonari R; Kamura T
TI -
[Treatment of malignant ovarian germ cell tumor and sex cord tumors]
SO - Gan To Kagaku Ryoho 2002 Aug;29(8):1358-62
AD - Department of Obstetrics and Gynecology, Iwate Medical University, 19-1
Uchimaru, Morioka, 020-8505, Japan.
We outline chemotherapy mainly for malignant ovarian germ cell and
sex-cord tumors, based on studies in the literature and our own clinical
experiences. With both tumors, PEB treatment is standard adjuvant
chemotherapy. With regard to the number of dosage courses, 4 courses are
regarded as tolerable after incomplete reduction, and 3 courses as
adjuvant treatment after complete extraction. This chemotherapy is
effective for preservation of fertility in young patients with malignant
ovarian germ cell tumor. In both tumors, some cases show chemotherapy
resistance. An effective second-line treatment strategy using a new
anticancer agent needs to be established for such cases in the future.
13
UI - 12183965
AU - Finnish Gynecological Association
TI -
[Ovarian cancer]
SO - Duodecim 2001;117(22):2318-32
14
UI - 12168878
AU - Takano M; Kikuchi Y; Kita T; Suzuki M; Ohwada M; Yamamoto T; Yamamoto K;
TI -
Inoue H; Shimizu K
Phase I and pharmacological study of single paclitaxel administered
weekly for heavily pre-treated patients with epithelial ovarian cancer.
SO - Anticancer Res 2002 May-Jun;22(3):1833-8
AD - Department of Obstetrics and Gynecology, National Defense Medical
College, Saitama, Japan.
We have reported that paclitaxel results in cisplatin sensitization in
cisplatin-resistant ovarian cancer cell lines in vitro and in nude mice.
The purpose of this trial was to determine the maximum tolerated dose
and recommend phase II dose of weekly single agent paclitaxel for
outpatients with recurrent or persistent epithelial ovarian carcinoma
(REOC), with standard chemotherapy containing platinum in the initial
setting. Patients with REOC were eligible for this protocol regardless
of the number and kind of previous chemotherapy regimens. The starting
dose was paclitaxel 70 mg/m2/week in 1-hour infusion, 3 weeks on, 1 off
and repeated at least twice. This dose was increased by 10 mg per step
to 100 mg/m2/week. Three patients were accrued to each dose cohort.
Three new patients were to be entered at escalation doses unless
dose-limiting toxicities (DLT) occurred, defined as grade 4
hematological or grade 3/4 non-hematological toxicities. If 1 out of 3
patients developed DLT, 3 additional patients were entered at the same
dose level. Sixteen patients were accrued. All the patients had received
at least one prior platinum-containing regimen (1 regimen 14 cases, 2
regimens 1 case, 3 regimens 1 case). At the level I dose of 70
mg/m2/week no hematological or non-hematological toxicity more than
grade 2 was observed. At the level II dose of 80 mg/m2/week, 1 patient
had grade 4 non-hematological toxicity, showing difficulty-walking.
Three new additional patients were treated with the same dose. Except
for this patient, 1 had grade 3 leukopenia and grade 4 neutropenia, but
these toxicities were overcome within 3 days without support of
granulocyte-colony stimulating factor (G-CSF). At the level III dose, 90
mg/m2/week, 1 of 3 patients showed grade 4 leukopenia and 2 had grade 4
neutropenia, requiring support by G-CSF. Similarly, when using 100
mg/m2/week of paclitaxel, 2 out of 4 patients had more than grade 3
hematological toxicity. However, at levels II or IV, no
non-hematological toxicity exceeding grade 2 was observed. Even if the
weekly single paclitaxel was repeated, the toxicity did not seem to
accumulate. According to dose-escalation, use of G-CSF and treatment
delay were increased. The use of G-CSF was significantly (p<0.05)
increased between levels I, II, III and IV. Although treatment with 90
or 100 mg/m2/week, at 3 weeks on, 1 off was tolerable and safe with
support of G-CSF, these doses cannot be recommended for out-patients
because of treatment delay. In this phase I trial, 80 mg/m2/week of
paclitaxel was recommended as the phase II dose for outpatients.
15
UI - 12009393
AU - Hasenburg A; Fischer DC; Tong XW; Rojas-Martinez A; Kaufman RH; Ramzy I;
TI -
Kohlberger P; Orlowska-Volk M; Aguilar-Cordova E; Kieback DG
Adenovirus-mediated thymidine kinase gene therapy for recurrent ovarian
cancer: expression of coxsackie-adenovirus receptor and integrins
alphavbeta3 and alphavbeta5.
SO - J Soc Gynecol Investig 2002 May-Jun;9(3):174-80
AD - Department of Obstetrics and Gynecology, University Medical Center,
Hugstetter Strasse 55, 79106 Freiburg/Brsg., Germany.
ahasenb@frk.ukl.uni-freiburg.de
OBJECTIVE: Ten patients with recurrent ovarian cancer received a
combined treatment of optimal tumor debulking, adenovirus-mediated
herpes simplex virus thymidine kinase gene therapy (GT), and systemic
application of acyclovir or valacyclovir and topotecan. Biopsies were
taken at the time of secondary debulking about 1 month after the
application of GT and chemotherapy and were analyzed for expression of
coxsackie-adenovirus receptor (CAR) and integrins alphavbeta3 and
alphavbeta5 with respect to treatment response. METHODS: Treatment
modalities and study design have been described recently.
Immunohistochemistry was used to visualize expression of CAR and
integrins alphavbeta3 and alphavbeta5 in tumor samples taken before and
after application of GT. RESULTS: Before GT six of ten patients
presented with CAR-positive and four with CAR-negative tumors. After GT
all tumors showed CAR expression. Integrin alphavbeta3 was found in all
tumors before and after GT. Expression of integrin alphavbeta5 was seen
in eight of ten tumor samples before GT and in all samples after GT.
CONCLUSION: Despite the importance of CAR and integrin expression for
successful adenovirus internalization, other cell surface receptors
might be involved in this process. It is too early to decide whether
expressions of CAR and integrin alphavbeta3/alphavbeta5 on tumor cells
are appropriate additional inclusion criteria for the enrollment of
patients in GT trials. Further research is necessary to evaluate the
effect of GT plus chemotherapy on CAR and integrin expression.
16
UI - 12210444
AU - Stern JW; Bunin N
TI -
Prospective study of carboplatin-based chemotherapy for pediatric germ
cell tumors.
SO - Med Pediatr Oncol 2002 Sep;39(3):163-7
AD - Division of Oncology, The Children's Hospital of Philadelphia and The
University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
julie.stern@lvh.com
BACKGROUND: Survival of pediatric patients with malignant germ cell
tumors has improved dramatically with the use of cisplatin-based
chemotherapy, though patients are at high risk of significant long-term
complications. In a prospective study, carboplatin was substituted for
cisplatin in an attempt to minimize nephro- and oto-toxicities, while
achieving excellent disease-free survival. PROCEDURE: All consecutive
patients with malignant germ cell tumors at The Children's Hospital of
Philadelphia were treated between 1989 and 1998. After pathologic
confirmation of disease and pretreatment evaluation of pulmonary, renal,
and otologic function, patients received etoposide 150 mg/m(2) days 1,
2, 3; carboplatin 600 mg/m(2) day 2; and bleomycin 10 mg/m(2) day 3 for
at least four courses. RESULTS: Twenty-three patients were entered for
study, and were available for evaluation. All patients achieved either a
complete or partial remission following therapy with surgery and
chemotherapy. With a median of 58 months of follow-up, overall survival
is 91% and event-free survival is 87%. Therapy was given as an
outpatient, and well tolerated, with 20 admissions for fever and
neutropenia. Ototoxicity and nephrotoxicity, when evaluated, have been
extremely limited. Three patients, all with stage III disease, have
relapsed; one of these remains alive and disease free. CONCLUSIONS:
Carboplatin can successfully substitute for cisplatin during the
treatment of pediatric germ cell tumors without sacrificing response or
survival. Long-term effects, especially nephrotoxicity and ototoxicity,
were rare or mild among the small number of patients evaluated.
Carboplatin appears to be a safe and efficacious alternative in the
treatment of germ cell tumors, and should be considered as primary
therapy for pediatric patients. Copyright 2002 Wiley-Liss, Inc.
17
UI - 12187066
AU - Sugiyama T; Yakushiji M; Kamura T; Ikeda M; Umesaki N; Hasegawa K;
TI -
Ishikawa M; Saji F; Hiura M; Takahashi T; Sato S; Ochiai K; Kikkawa F;
Takeuchi S; Ohashi Y; Noda K; Japan CPT-11 Study Group
Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for
advanced ovarian cancer.
SO - Oncology 2002;63(1):16-22
AD - Department of Obstetrics and Gynecology, Kurume University School of
Medicine, Kurume City, Japan. sugisama@med.kurume-u.ac.jp
OBJECTIVE: To evaluate the efficacy and toxicity of a combination of
irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced
ovarian cancer. METHODS: Twenty-six patients with previously untreated
advanced epithelial ovarian cancer were enrolled in this study. CPT-11
60 mg/m(2) was administered intravenously on days 1, 8, and 15 in
combination with cisplatin 60 mg/m(2) on day 1. Cycles were repeated
every 28 days for at least two cycles. The median patient age was 55
years (range, 37-75), and the median performance status was 1. RESULTS:
Objective responses were recorded in 19 of 25 eligible patients (76%;
95% confidence interval, 55-91%). Complete responses were obtained in 2
patients (8%), and partial response in 17 patients (68%). Stable disease
was recorded in 2 patients (8%) and progressive disease in 2 (8%). The
median time to response was 62 days (range, 28-234 days). The median
survival time for all 25 patients was 30.9+ months (range, 4.1-60.0+
months). The major toxic effects were leukopenia, neutropenia, and
diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in
17 (68%), 20 (83.3%), and 5 patients (20%), respectively.
Thrombocytopenia was less common. No treatment-related deaths occurred.
CONCLUSION: The combination of CPT-11 and cisplatin showed significant
activity in chemotherapy-naive patients with advanced ovarian cancer.
Neutropenia was the dose-limiting adverse effect, whereas diarrhea was
mainly mild to moderate. Copyright 2002 S. Karger AG, Basel
18
UI - 12060445
AU - Fujiwara K; Suzuki S; Yoden E; Ishikawa H; Imajo Y; Kohno I
TI -
Local radiation therapy for localized relapsed or refractory ovarian
cancer patients with or without symptoms after chemotherapy.
SO - Int J Gynecol Cancer 2002 May-Jun;12(3):250-6
AD - Department of Obstetrics and Gynecology, Kawasaki Medical School, 577
Matsushima, Kurashiki-City 701-0192, Japan.
fujiwara@med.kawasaki-m.ac.jp
The purpose of this paper is to prospectively evaluate the effects of
local radiation therapy upon localized ovarian cancer following
chemotherapy. Patients with objective relapses or refractory disease but
with localized epithelial ovarian cancers and who had undergone at least
one regimen of chemotherapy were enrolled in this study. External
irradiation was performed on all patients. Twenty patients, with a mean
age of 53.8 +/- 10.3 y, were enrolled in this study. The median number
of previous chemotherapies was 2. The interval between previous
chemotherapy and radiation therapy was 4.5 months. The maximum diameter
of the lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3
Gy. Neither hematologic nor intestinal toxicity >grade 3 was observed.
Forty-four disease sites, including the lymph nodes, vaginal cuff,
pelvis, abdomen, subcutaneous regions, and the brain were irradiated.
Thirty of these sites were symptom-free before irradiation. In patients
with symptoms, the symptomatic relief was obtained in approximately 50%
of patients. Smaller lesions (P = 0.024) and lymph nodes (P = 0.042)
demonstrated better responses than larger lesions or other sites,
respectively. Regression rates correlated with longer survivals (P =
0.0195) after radiation therapy. Survival was significantly better when
radiation therapy was given before patients had symptoms (P = 0.001).
Survival was also better in patients with lymph node disease only (P =
0.0069). We conclude that local radiation therapy may be one of the
treatment options for relapsed or refractory but localized ovarian
cancer, particularly when the tumor is small and/or located in the lymph
nodes, even when patients had no symptoms.
19
UI - 12133408
AU - Yuan B; Mi R
TI -
[Antisense oligodeoxynucleotides of human telomerse catalytic sub-unit
inhibits telomerase activity and proliferation in SKOV3 and COC1]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 Apr;37(4):198-201
AD - Department of Obstetrics and Gynecology, General Hospital of Tianjin
Medical University, Tianjin 300052, China.
OBJECTIVE: To study the effects of antisense oligodeoxynucleotides (ODN)
of hEST2 (AODN) on telomerase activity and proliferation in ovarian
cancer cell lines SKOV3 and COC1. METHODS: Antisense and sense human
telomerse catalytic sub-unit (hEST2) phosphorothioate (SODN) and random
ODN were designed, synthesized and transfected into SKOV3 and COC1 cells
by lipofectamine. The expression of hEST2 mRNA and telomerase activity
in SKOV3 and COC1 were tested by reverse transcription-polymerase chain
reaction and telomeric repeat amplification protocol before and after
transfection. The proliferation and growth in SKOV3 and COC1 were also
investigated by methyl thiazolyl tetrazolium and growth curve before and
after transfection. RESULTS: AODN could down-regulate the expression of
hEST2 mRNA, inhibit telomerase activity and proliferation of ovarian
cell lines. The efficiency depends on dose and period of administration.
At 48 h, 30 micromol/L AODN had the highest activity. The expression of
hEST2 mRNA were declined 54.6% and 44.6% in SKOV3 and COC1 respectively.
And also the inhibition of telomerase activity were 47.9% and 42.7%
respectively in the two cell lines. CONCLUSIONS: AODN of hEST2 clearly
inhibited the proliferation of ovarian cancer cell lines. hEST2 may thus
be a new target of gene therapy in ovarian carcinoma.
20
UI - 12133409
AU - Wang C; Hu F; Lu Y; Wang S; Ma D
TI -
[Effects of RelA antisense oligonucleotide on apoptosis of ovarian
cancer cells COC1]
SO - Zhonghua Fu Chan Ke Za Zhi 2002 Apr;37(4):202-4
AD - Department of Obstetrics and Gynecology, Tongji Hospital of Tongji
Medical College, Huazhong Science and Technology University, Wuhan,
430030, China.
OBJECTIVE: To evaluate the effects of RelA antisense oligonucleotide on
apoptosis of ovarian cancer cells. METHODS: COC1 cell line was treated
with RelA antisense oligonucleotide combining with tumor necrosis factor
(TNF)-alpha or paclitaxel at appropriate concentrations and duration.
The apoptosis and RelA activation of ovarian cancer line COC1 cell were
measured by indirect immunofluorescence, Western blot, flow cytometric
analysis, DNA ladder assay. RESULTS: The apoptosis increased obviously
in COC1 rells if treated by RelA antisense oligonucleotide combining
with paclitaxel 50 micromol/L than paclitaxel 50 micromol/L only (27.4
+/- 0.5)% vs (12.3 +/- 0.6)% (P < 0.01), when treated 12 hs; (31.7 +/-
0.3)% vs (13.0 +/- 0.5)% (P < 0.01) when treated 24 hs. The apoptosis
was also increased obviously in COC1 cells if treated by RelA antisense
oligonucleotide combining with TNF-alpha 50 microgram/L than TNF-alpha
50 microgram/L alone. (30.8 +/- 0.3)% vs (13.2 +/- 0.4)% (P < 0.01).
CONCLUSION: RelA antisense oligonucleotide may induce apoptosis
susceptibility of COC1 cells to TNF-alpha or paclitaxel.
21
UI - 12168915
AU - Ness RB; Wisniewski SR; Eng H; Christopherson W
TI -
Cell viability assay for drug testing in ovarian cancer: in vitro kill
versus clinical response.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1145-9
AD - Graduate School of Public Health, University of Pittsburgh, PA 15261,
USA.
Several methods have been and are in use for assessing the in vitro
sensitivity and resistance of an individual woman's tumor cells. We
report the predictive accuracy of an optimized chemoresponsiveness test.
PATIENTS AND METHODS: In a retrospective chart review of 18 women with
late stage, papillary serous ovarian cancer undergoing 21 episodes of
chemotherapy, we assessed the correlation between the results of this
test, the ChemoFx Assays, and clinical response. RESULTS: The positive
predictive value of the ChemoFx Assay was 63.6% and the negative
predictive value was 100%. Survival curves among women with good vs.
poor response on the chemoresponse test showed an early, albeit
non-significant survival advantage among women whose tumors tested
sensitive to the chemotherapeutic regimens used. CONCLUSION: This study
suggests that optimized chemoresponse assays may be beneficial in
selecting specific chemotherapy regimens for women with ovarian cancer.
22
UI - 12168916
AU - Vuento MH; Salmi TA; Remes KJ; Grenman SE
TI -
Hematological toxicity of salvage treatment after high-dose chemotherapy
and conventional chemotherapy of ovarian cancer.
SO - Anticancer Res 2002 Mar-Apr;22(2B):1151-5
AD - Departments of Obstetrics and Gynecology, Turku University Central
Hospital, Finland.
BACKGROUND: To compare the toxicity of salvage chemotherapy (CT) given
for recurrent or progressive ovarian cancer (OC) after either high-dose
chemotherapy (HDC) or conventional CT. PATIENTS AND METHODS: HDC
supported by autologous stem cell transplantation was given to ten OC
patients. Seven of them were treated with salvage CT for recurrent
disease and were included in this study (Group A). Seven patients with
recurrent OC treated primarily with conventional CT (Group B) were
matched for age (+/- 3 years), stage and histology. The hematological
toxicity of treatment was graded according to the WHO criteria. RESULTS:
During salvage CT, grade 3-4 neutropenia was seen in nine out of 81
courses (11.1%) in Group A and in six out of 85 courses (7.1%) in Group
B (p <0.1). The use of G-CSF was more common in Group A than in Group B,
both during first-line and salvage CT. When the mobilisation courses
were excluded in Group A, the use of G-CSF was more common during
salvage treatment than during primary treatment (27 out of 81 vs. 16 out
of 85, p < 0.05). Also, in Group B the use of G-CSF was more common
during salvage CT than during primary treatment (10 out of 85 vs. 0 out
of 73, p < 0.01). Grade 3-4 thrombocytopenia was seen in nine out of 81
courses (11.1%) in Group A but in none of the 85 courses (0%) in Group B
(p<0.05). No platelet transfusion was needed during salvage treatment.
The mean interval of courses in salvage CT was 27.7 days (range 19-71)
in Group A and 27.5 days (range 18-120) in Group B (p = ns). Overall
survival was 40.4 months in Group A and 33.0 months in Group B (p <
0.1). CONCLUSION: Salvage treatment after HDC was well-tolerated when
given with G-CSF support. Salvage chemotherapy could be carried out with
the same doses and intervals both for patients treated earlier with HDC
and conventional CT.
23
UI - 12209708
AU - Seidman JD; Kurman RJ
TI -
Treatment of micropapillary serous ovarian carcinoma (the aggressive
variant of serous borderline tumors).
SO - Cancer 2002 Aug 15;95(4):675-6
24
UI - 12209723
AU - Bristow RE; Gossett DR; Shook DR; Zahurak ML; Tomacruz RS; Armstrong DK;
TI -
Montz FJ
Recurrent micropapillary serous ovarian carcinoma.
SO - Cancer 2002 Aug 15;95(4):791-800
AD - The Kelly Gynecologic Oncology Service, Department of Gynecology and
Obstetrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland
21287-1246, USA. rbristo@jhmi.edu
BACKGROUND: The objectives of the current study were to: 1) characterize
the clinical outcome of patients with recurrent micropapillary serous
ovarian carcinoma (MPSC) and 2) evaluate the survival impact of
secondary cytoreductive surgery and other prognostic variables. METHODS:
Twenty-six patients with recurrent MPSC were identified retrospectively
from hospital and tumor registry databases. Survival curves were
generated from the time of tumor recurrence using the Kaplan-Meier
method and statistical comparisons were performed using the log-rank
test, logistic regression analysis, and the Cox proportional hazards
regression model. RESULTS: The median age of the patients at the time of
recurrence was 46 years. The mean progression-free interval was 31.6
months, and 92% of patients had advanced stage disease at the time of
the initial diagnosis. Twenty-one patients underwent secondary
cytoreductive surgery; tumor debulking was performed in 90.5% of cases
and 52.4% of patients required an intestinal resection. Optimal
resection (residual disease < or = 1 cm) was achieved in 15 patients
(71.4%). Patients undergoing optimal secondary cytoreduction had a
median survival time of 61.2 months from the date of disease recurrence,
compared with 25.5 months for those patients in whom suboptimal residual
disease remained (P < 0.02) and 29.9 months for nonsurgical patients (P
< 0.01). On multivariate analysis, optimal secondary cytoreduction was
found to be the only independent predictor of survival. Salvage
chemotherapy produced an objective response in 25% of patients with
measurable disease. The administration of chemotherapy prior to surgical
intervention was associated with a trend toward worse survival and a
lower likelihood of optimal secondary cytoreduction. CONCLUSIONS:
Optimal secondary cytoreductive surgery is feasible in the majority of
patients with recurrent MPSC and is an independent predictor of
subsequent survival. Surgical intervention should be considered for
those patients with recurrent MPSC. [See editorials on pages 675-6 and
677-80, this issue.] Copyright 2002 American Cancer Society.DOI
10.1002/cncr.10789
25
UI - 11994764
AU - Patyanik M; Mayer A; Polgar I
TI -
Results of ovary tumor treatment with abdominally administered (198)Au
evaluated on the basis of long term follow up.
SO - Pathol Oncol Res 2002;8(1):54-7
AD - Uzsoki Hospital Uzsoki utca 29, Budapest, 1145, Hungary.
In the period between 1959 and 1980 165 patients previously operated
with ovarian tumor were treated by intraperitoneally administered
(198)Au in the Oncoradiological Centre of the Uzsoki Hospital. The stage
distribution of the 158 patients with common epithelial histology was as
it follows: Stage I/A 31; Stage I/B 9; Stage I/C 59; Stage II/A 19;
Stage II/B 11; Stage II/C 7, Stage III/A 22. The five year survival
result is the next: Stage I/A 90%; Stage I/B 78%; Stage I/C 58%; Stage
II/A 26%; Stage II/B 27%; Stage II/C 14%; Stage III/A 18%. From the
other 7 patients six had sex cord tumor and one lipid cell tumor. The
number of the side effects is in good agreement with the data in
literature. The use of (198)Au for intraperitoneal treatment of ovary
tumors is not contemporary today because of gamma radiation of
radiogold, but intraperitoneal radiation treatment should not be
forgotten.
26
UI - 12109222
AU - Schmidbauer S; Sitzmann G; Trupka A; Hallfeldt KK
TI -
[Laparoscopic colostomy: experience in patients with ovarian or
ano-rectal cancer, non-operable or with rectovaginal fistula]
SO - G Chir 2002 Mar;23(3):101-3
AD - Chirurgische Klinik und Poliklinik, Klinikum Innestadt
Ludwig-Maximilians Universitaet Muenchen.
carried out in 23 patients with advanced ovarian cancer, inoperable
carcinoma of the anorectum or rectovaginal fistulas. There were no
intraoperative or postoperative complications and postoperative recovery
was rapid with all patients having function of the colostomy within 24
hrs and regaining their preoperative state of mobility on the second
postoperative day. The laparoscopic approach allows the careful
selection of the colostomy site, easy mobilisation of the colon, causing
only little disruption to the intestinal function hence improving
postoperative recovery. From Authors' experience, laparoscopic colostomy
is a simple and safe operation in most cases and can be used as the
preferred technique of intestinal diversion.
27
UI - 12132060
AU - Gottschalk A; Freitag M; Burmeister MA; Becker C; Horn EP; Standl T
TI -
Patient-controlled thoracic epidural infusion with ropivacaine 0.375%
provides comparable pain relief as bupivacaine 0.125% plus sufentanil
after major abdominal gynecologic tumor surgery.
SO - Reg Anesth Pain Med 2002 Jul-Aug;27(4):367-73
AD - Department of Anesthesiology, University Hospital Eppendorf, Hamburg,
Germany. andregottschalk@hotmail.com
BACKGROUND AND OBJECTIVES: We tested the hypothesis that an opioid-free
local anesthetic alone is able to provide comparable analgesia to the
opioid supplemented epidural application of local anesthetics using
thoracic epidural catheters after major abdominal surgery. METHODS: In a
prospective, randomized, and double-blind study, we have compared the
analgesic efficacy and side effects of ropivacaine 0.375% (group R)
versus bupivacaine 0.125% in combination with sufentanil 0.5
microg/mL(-1) (group B/S) via a thoracic epidural catheter for a
duration of 96 hours after major abdominal surgery in 30 gynecologic
tumor patients. Piritramide was given for breakthrough pain. Assessments
were performed every 12 hours after start of the epidural infusion using
continuous (first 24 hours) and patient-controlled epidural analgesia
(PCEA) (24 to 96 hours). RESULTS: No differences were seen in
demographic and perioperative data. Dynamic pain scores (visual analog
scale [VAS] values) were comparable between groups during mobilization
(group R v group B/S: 24 hours: 40 +/- 30 v 36 +/- 14, P =.9; 48 hours:
46 +/- 33 v 42 +/- 25, P =.93; 72 hours: 42 +/- 24 v 48 +/- 26, P =.78;
96 hours: 42 +/- 25 v 29 +/- 28, P =.49) and on coughing during the
whole study period. Hemodynamics, intensity of motor block (Bromage
scale), and side effects like nausea, vomiting, pruritus, and bladder
disfunction also did not differ between groups. CONCLUSION: The present
study shows that thoracic epidural infusion of ropivacaine 0.375%
provides comparable pain relief and incidence of side effects after
major abdominal gynecologic surgery as bupivacaine 0.125% in combination
with 0.5 microg/mL(-1) sufentanil and may therefore represent an
alternative in epidural pain management.
28
UI - 12144679
AU - Griffiths CT; Parker LM; Lee S; Finkler NJ
TI -
The effect of residual mass size on response to chemotherapy after
surgical cytoreduction for advanced ovarian cancer: long-term results.
SO - Int J Gynecol Cancer 2002 Jul-Aug;12(4):323-31
AD - Dana Farber Cancer Institute, the Brigham & Women's Hospital, Boston,
MA, USA.
We report an observational study of chemotherapeutic regression of
ovarian tumor implants according to decrements in residual mass size
after surgical cytoreduction. Cytoreductive operations were attempted on
74 consecutive patients with stages IIIB-IV disease referred for this
purpose. Thirty-two patients had received one to four courses of
preoperative chemotherapy (22 responses, no progressions). Postoperative
chemotherapy followed current protocols at Dana Farber Cancer Institute
(n=61) or referring institutions (n=13); 57 regimens contained
cisplatin. Postchemotherapy response was assessed clinically or by
second-look procedures. Negative findings were considered a complete
remission. Masses > 1 cm were excised from 62 patients. Twelve patients
were inoperable. Twenty-eight patients had complete remissions and the
correlation between these and decrements in residual mass size was
highly significant (P < 0.0001). Complete remissions had a uniform
effect and were the only outcome predictive of survival. Preoperative
treatment greatly facilitated cytoreduction but only masses 0-0.2 cm
were sensitive to postoperative chemotherapy. Masses 0.5 cm or less were
optimal. They made up 77% of operable patients and supplied 25 (89%) of
the complete remissions. Cytoreduction is not always required but even
large-volume disease in the upper abdomen can be safely excised. The
concept that masses larger than 10 cm indicate general chemoresistance
has not been sustained.
29
UI - 12144680
AU - Kitchener HC
TI -
Clinical practice guidelines: loss of clinical freedom or a coming of
age?
SO - Int J Gynecol Cancer 2002 Jul-Aug;12(4):332-6
AD - Academic Unit of Obstetrics and Gynaecology, St. Mary's Hospital,
Whitworth Park, Manchester M13 0JH, United Kingdom.
hkitchener@central.cmht.nwest.nhs.uk
When a woman presents to us with gynecological cancer our duty is to
offer the most effective means of treatment; that which maximizes the
potential for cure at the same maintaining or improving quality of life.
For the majority of our patients we are able to contemplate cure but for
many, particularly those with advanced ovarian cancer, this will not be
possible although we can provide the prospect of several years of
survival. In an international context our ability to provide optimal
care depends largely on the healthcare resources which are affordable,
and although in many parts of the world these are very limited, the same
principles apply. This series of articles will put the spotlight on
effective care in gynaecological oncology following an evidence based
theme. The articles will be informative, punchy and provocative. The
first of these contributions looks at clinical guidelines: what are they
for, how do we produce them
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