National Cancer Institute®
Last Modified: March 1, 2002
UI - 10995813
AU - Vergote I; Rustin GJ; Eisenhauer EA; Kristensen GB; Pujade-Lauraine E;
TI - Parmar MK; Friedlander M; Jakobsen A; Vermorken JB Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup.
SO - J Natl Cancer Inst 2000 Sep 20;92(18):1534-5
UI - 11778075
AU - Pierelli L; Perillo A; Ferrandina G; Salerno G; Rutella S; Fattorossi A;
TI - Battaglia A; Rughetti A; Nuti M; Cortesi E; Leone G; Mancuso S; Scambia G The role of growth factor administration and T-cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G-CSF and GM-CSF.
SO - Transfusion 2001 Dec;41(12):1577-85
AD - Hematology and Hemotransfusion Service, Institute of Obstetrics and Gynecology, Sacred Heart Catholic University, Rome, Italy. firstname.lastname@example.org
BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival. RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G-CSF and GM-CSF series. Conversely, significantly higher T-cell counts were observed in G-CSF-treated patients during the early and late posttransplant follow-up. Patients who received G-CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G-CSF-treated patients encourages the use of G-CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM-CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT.
UI - 11865633
AU - Furue H; Ikeda M; Tsukagoshi S; Taguchi T; Fujii T; Rikimaru T
TI - [Clinical usefulness of ondansetron injection in patients receiving cancer chemotherapy]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):261-71
AD - Teikyo University.
Before and after launch of 5-HT3, antagonist, necessary dose and duration of chemotherapy were compared between the patients who were confirmed to have undergone chemotherapy before the launch of 5-HT3 antagonist (retrospective group) and the ones currently using ondansetron (OND) for chemotherapy-induced emesis (prospective group). Clinical usefulness of OND was evaluated through survey on quality of life (QOL) to patients and questionnaires to physicians, nurses & patients. Necessary dose of chemotherapy was evaluated by investigating actual dose of cisplatin (CDDP). As the result, necessary dose of CDDP was confirmed to be different between retrospective and prospective groups. The influence on the actual CDDP dose was observed with or without use of G-CSF or by recommended dose of CDDP, while no influence by 5-HT3 antagonist was observed. For necessary duration of chemotherapy, significant difference was not observed between retrospective or prospective groups. On the other hand, actual CDDP dose or necessary duration of chemotherapy were confirmed to be greatly affected by chemotherapy-induced adverse events such as blood disorder (e.g. bone marrow suppression) or renal disorder, rather than chemotherapy-induced emesis. As the result of QOL survey to patients and other questionnaires to medical staff & patients, the fact of chemotherapy-induced emesis to lower the patient's QOL as well as the importance of emetic control was confirmed. It was also confirmed that the workload of nurses or other medical staff has lessened since the launch of 5-HT3 antagonists.
UI - 11750848
AU - Vignati S; Codegoni A; Polato F; Broggini M
TI - Trail activity in human ovarian cancer cells: potentiation of the action of cytotoxic drugs.
SO - Eur J Cancer 2002 Jan;38(1):177-83
AD - Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy.
The ability of the TRAIL ligand to induce cell killing in three ovarian cancer cell lines was investigated using a glutathione-S-transferase (GST)-TRAIL fusion protein. One of the three lines was sensitive to TRAIL, which induced cell killing in a range of concentrations similar to those necessary to kill the TRAIL-sensitive leukaemic cell line Jurkat. The relative mRNA expression of the four TRAIL receptors did not explain the different sensitivities of the three ovarian cancer cell lines to TRAIL treatment. The TRAIL-sensitive IGROV-1 cell line expressed slightly lower levels of the anti-apoptotic protein FLIP than the two TRAIL-insensitive cell lines (A2780 and SKOV-3). Nevertheless, although TRAIL did not significantly reduce cell growth in the A2780 and SKOV-3 cells it did enhance the activity of paclitaxel and cisplatin (DDP), the two most widely used drugs for the treatment of ovarian cancer, increasing their ability to induce apoptosis. The use of TRAIL in combination with classical anticancer agents might thus boost the apoptotic response, improving the activity of DDP and paclitaxel in ovarian cancer.
UI - 11823695
AU - Plaxe SC; Blessing JA; Morgan MA; Carlson J; Gynecologic Oncology Group
TI - Phase II trial of pyrazoloacridine in recurrent platinum-resistant ovarian cancer: a Gynecologic Oncology Group study.
SO - Am J Clin Oncol 2002 Feb;25(1):45-7
AD - Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California-San Diego Medical Center, 402 Dickinson Street, San Diego, CA 92103-8433, U.S.A.
The Gynecologic Oncology Group performed a Phase II study to determine the response rate of pyrazoloacridine (PZA) in patients with platinum-resistant ovarian cancer. PZA was administered at a dose of 750 mg/m2 intravenously over 3 hours every 3 weeks. Among 24 evaluable patients, there was 1 (4.2%) complete and 1 (4.2%) partial response. The major toxicities were hematologic. With the dose and schedule used, PZA had only modest activity in this population.
UI - 11857006
AU - van der Burg ME; de Wit R; van Putten WL; Logmans A; Kruit WH; Stoter G;
TI - Verweij J Weekly cisplatin and daily oral etoposide is highly effective in platinum pretreated ovarian cancer.
SO - Br J Cancer 2002 Jan 7;86(1):19-25
AD - Department of Medical Oncology, Rotterdam Cancer Institute and University Hospital, Rotterdam, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
We investigated the potential of weekly cisplatin and daily oral etoposide followed by oral etoposide maintenance therapy in patients with platinum-refractory ovarium cancer. One hundred and seven patients were entered on the study, 98 patients completed the induction therapy consisting of cisplatin at either 50 or 70 mg m(-2) weekly for six administrations plus oral etoposide at a dose of 50 mg daily. Of these 98 patients, 38 had a platinum treatment-free interval of more than 12 months, 32 had an interval between 4 and 12 months, and 28 had progressed during or within 4 months after last platinum therapy. We assessed response rates and time to progression, and also response duration and survival. Analyses were done on the 98 evaluable patients. All 107 patients were considered evaluable for toxicity. Of the 38 patients with a treatment-free interval of more than 12 months, 92% responded, with 63% complete responses. The median progression-free survival in these patients was 14 months, and the median survival was 26 months. Of the 32 patients with an interval of 4-12 months, 91% responded, with 31% complete responses, a median progression-free interval of 8 and a median overall survival of 16 months. Of the 28 patients with platinum-refractory disease, 46% as yet responded, with 29% complete responses, median progression-free interval of 5 and an overall survival of 13 months. Haematologic and non-haematologic, particularly renal toxicity and neurotoxicity, were notably mild. We conclude that this intensive regimen of weekly cisplatin plus daily etoposide is highly effective and well tolerated in patients with ovarian cancer relapsing after conventional platinum-based combination chemotherapy, including patients who have progressed during or within 4 months after platinum treatment.
UI - 11683313
AU - Fitch MI; Gray RE; Franssen E
TI - Perspectives on living with ovarian cancer: older women's views.
SO - Oncol Nurs Forum 2001 Oct;28(9):1433-42
AD - Toronto-Sunnybrook Regional Cancer Centre, Ontario, Canada. email@example.com
PURPOSE/OBJECTIVES: To describe the perspectives of older women regarding their experiences living with ovarian cancer. DESIGN: Retrospective survey. SETTING: Canada. SAMPLE: 146 women, 61 years of age or older, diagnosed with ovarian cancer. METHODS: Questionnaire distributed by oncologists and nurses in 26 cancer clinics across Canada to eligible patients during a six-week period. MAIN RESEARCH VARIABLES: Patient problems experienced, help received for problems, impact of illness, quality of life, importance of and satisfaction with information received, and helpfulness of others. FINDINGS: Women experienced, on average, 5.2 problems since diagnosis. The most frequently identified problems were side effects (54%), fear of recurrence (45%), bowel difficulties (43%), and difficulty sleeping (36%). Of the women who experienced problems, the proportion who felt they received adequate help ranged from 36%-74%. Approximately half (57%) of these women reported a lifestyle change. A significant difference was observed in quality of life before and after the diagnosis of ovarian cancer (p = 0.0002). When asked about the desire to talk about their difficulties with cancer, only 54% indicated that they wanted to talk. Approximately one-quarter of the women were satisfied with the information they received regarding complementary (25%) and alternative (23%) therapies, and how to speak with other women living with ovarian cancer (28%). Thirty-five percent were satisfied with the information they received about self-help groups. CONCLUSION: Ovarian cancer has a significant impact on older women, and many perceive they are not receiving adequate assistance for problems they experience. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses should conduct comprehensive assessments of the needs of older women with ovarian cancer, refer those who require specialized counseling, and provide information desired by patients with ovarian cancer about available resources.
UI - 11750835
AU - Sparreboom A; de Jonge MJ; Verweij J
TI - The use of oral cytotoxic and cytostatic drugs in cancer treatment.
SO - Eur J Cancer 2002 Jan;38(1):18-22
AD - Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, 3075 EA Rotterdam, The Netherlands. firstname.lastname@example.org
Although with a few exceptions, most new anticancer agents are initially developed for intravenous use, oral treatment with anticancer agents is, if feasible, to be preferred, as this route of administration is convenient to patients, reduces administration costs and facilitates the use of more chronic treatment regimens. Recent studies have identified various physiological barriers limiting the oral absorption of anticancer drugs. Presently, several strategies are explored to alter the low and variable oral bioavailability of several important anticancer agents by taking advantage of an intentional interaction between anticancer agents and drugs that modulate active intestinal drug transporters or (intestinal) enzymes.
UI - 11750840
AU - Gore M; Oza A; Rustin G; Malfetano J; Calvert H; Clarke-Pearson D;
TI - Carmichael J; Ross G; Beckman RA; Fields SZ A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer.
SO - Eur J Cancer 2002 Jan;38(1):57-63
AD - Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. email@example.com
A multicentre, randomised study was carried out in Europe, South Africa and North America to compare the activity and tolerability of oral versus intravenous (i.v.) topotecan in patients with relapsed epithelial ovarian cancer. Patients who had failed first-line therapy after one platinum-based regimen, which could have included a taxane, were randomised to treatment with either oral (p.o.) topotecan, 2.3 mg/m(2)/day or i.v. topotecan 1.5 mg/m(2)/day for 5 days every 21 days. Patients were stratified by prior paclitaxel exposure, interval from previous platinum therapy and tumour diameter. 266 patients were randomised. Response rates were 13% orally (p.o.) and 20% (i.v.) with a complete response in 2 and 4 patients, respectively. The difference in the response rates was not statistically significant. Median survival was 51 weeks (p.o.) and 58 weeks (i.v.) with a risk ratio of death (p.o. to i.v. treatment) of 1.361 (95% confidence interval (CI): 1.001, 1.850). Median time to progression was 13 weeks (p.o.) and 17 weeks (i.v.). The principal toxicity was myelosuppression although grade 3/4 neutropenia occurred less frequently in those receiving oral topotecan. Toxicity was non-cumulative and infectious complications were relatively infrequent. Non-haematological toxicity was generally mild or moderate. The incidence of grade 3/4 gastrointestinal events was slightly higher for oral than i.v. topotecan. Oral topotecan shows activity in second-line ovarian cancer and neutropenia may be less frequent than with the i.v. formulation. A small, but statistically significant, difference in survival favoured the i.v. formulation, but the clinical significance of this needs to be interpreted in the context of second-line palliative treatment. Oral topotecan is convenient and well tolerated and further studies to clarify its role are ongoing.
UI - 11812075
AU - Perez-Gracia JL; Carrasco EM
TI - Tamoxifen therapy for ovarian cancer in the adjuvant and advanced settings: systematic review of the literature and implications for future research.
SO - Gynecol Oncol 2002 Feb;84(2):201-9
AD - Clinical Research Department, Eli Lilly and Company, Alcobendas, Madrid, Spain. firstname.lastname@example.org
BACKGROUND: Ovarian neoplasms frequently express hormonal receptors and are sensitive to hormonal manipulations, as shown by preclinical and clinical studies. However, despite the outstanding relevance of hormonal adjuvant therapy in breast cancer and the importance of receptor status as a predictive factor, few trials have addressed these issues in ovarian cancer. METHODS: Computerized and manual searches were performed to identify preclinical and clinical studies evaluating single-agent tamoxifen activity in ovarian cancer or any kind of hormonal therapy employed as adjuvant therapy for ovarian cancer. RESULTS: In advanced tumors, none of the trials was performed exclusively in chemonaive patients, but those including less heavily pretreated patients showed greater response rates. Some studies found a correlation between receptor status and activity (although differences were not significant), whereas other trials did not. Nevertheless, none were specifically designed to answer this question. Few randomized trials comparing hormonal treatment and chemotherapy versus chemotherapy alone were identified. Although their results were negative, all were small, and none was designed with the rigor that allowed adjuvant hormonal therapy to become successfully established in breast cancer. CONCLUSION: The activity of tamoxifen in advanced ovarian cancer has not been adequately evaluated and its role may have been underestimated. Furthermore, the relevance of adjuvant hormonal therapy in ovarian cancer and the predictive value of hormonal receptors have never been studied in well-designed trials. Additional studies to clarify the role of tamoxifen for this indication are warranted. B)2001 Elsevier Science.
UI - 11812079
AU - Bao R; Selvakumaran M; Hamilton TC
TI - Targeted gene therapy of ovarian cancer using an ovarian-specific promoter.
SO - Gynecol Oncol 2002 Feb;84(2):228-34
AD - Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
OBJECTIVES: The "suicide" gene therapy of cancer using promoters such as cytomegalovirus could cause severe toxicity to normal tissues due to a lack of specificity of prodrug activation. Therefore, we investigated gene therapy of ovarian cancer using ovarian-specific promoter (OSP1) to limit the synthesis of the prodrug activating enzyme HSVtk to ovarian cancer cells. METHODS: The HSVtk expressing plasmid pOSP1-HSVtk was created and transfected into an ovarian cancer cell line OVCAR3. The ganciclovir (GCV) sensitivity of the stable transfectants was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tissue specificity of this promoter was evaluated by comparing the sensitivity to GCV between ovarian and nonovarian cancer cell lines after they were transfected with pOSP1-HSVtk. One transfectant sensitive to GCV was implanted intraperitoneally to immunocompromised mice which were treated subsequently with GCV. Furthermore, this ovarian cancer survival model was used to evaluate the in vivo efficacy of cationic lipid mediated pOSP1-HSVtk gene delivery followed by GCV treatment. RESULTS: Stable transfectants of OVCAR3 cells bearing OSP1-HSVtk became more sensitive to GCV treatment compared to the parental cell line and vector transfected OVCAR3 cell line. OSP1-HSVtk could specifically sensitize the OVCAR3 ovarian cancer cell line to GCV. SCID mice transplanted with the OVCAR3 transfectant and treated with GCV survived longer than the mice without GCV treatment (P = 0.032). In vivo gene delivery mediated by a cationic lipid (GL67) followed by GCV treatment yielded a longer survival in the OVCAR3 survival model (P = 0.016). CONCLUSIONS: The OSP1 promoter can selectively direct suicide gene therapy of ovarian cancer and the in vivo efficacy is improved by using a cationic lipid GL67 as delivery vehicle as opposed to the direct injection of plasmid. B)2001 Elsevier Science.
UI - 11848519
AU - Gadducci A; Cosio S; Cionini L; Genazzani AR
TI - Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of advanced cervical cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3525-33
AD - Department of Procreative Medicine, University of Pisa, Italy. email@example.com
The role of chemotherapy in the management of advanced cervical cancer has been long debated. Whereas some phase II trials have shown promising results with neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to demonstrate any benefit with this sequential treatment in terms of loco-regional control and survival, mainly because chemotherapy could cause accelerated tumor clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant chemotherapy before surgery appear to be more promising. This treatment modality can increase the operability rate and reduce the incidence of positive nodes and other pathological risk factors. However, very few randomized trials comparing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus conventional irradiation treatment are currently available, whilst data about long-term survival of chemo-surgical-treated patients are scanty. Recently five prospective randomized trials compared concurrent cisplatin-based chemotherapy and irradiation versus hydroxyurea plus irradiation or irradiation alone. All showed a significant improvement in the outcome of patients treated with concurrent cisplatin-based chemoradiation. Based on these data, the National Cancer Institute released a Clinical Announcement stating that concurrent cisplatin-based chemoradiation should be the new standard of therapy for high-risk early stage and locally advanced cervical cancer. The introduction of taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and concurrent chemoradiation could further improve the results of these two treatment modalities. A multicenter randomized trial comparing chemo-surgical treatment with concurrent chemoradiation is warranted to better define the optimum therapeutic strategy for patients with advanced cervical cancer.
UI - 11848522
AU - Mobus V; Pfaff PN; Volm T; Kreienberg R; Kaubitzsch S
TI - Long time therapy with topotecan in patients with recurrence of ovarian carcinoma.
SO - Anticancer Res 2001 Sep-Oct;21(5):3551-6
AD - Department of Obstetrics and Gynecology, Stadtische Kliniken, Frankfurt, Germany. MoebusVolk@aol.com
BACKGROUND: In several phase II and III topotecan studies the large number of patients with stable disease is striking. Since no severe organ toxicity has been described for topotecan, long-term therapy with topotecan seems to be reasonable. In this summary we present evidence, that long-term topotecan therapy can be managed without cumulative hematological and non-hematological toxicity. PATIENTS AND METHODS: Thirty-three patients with recurrent ovarian cancer, who were treated with at least 7 courses of topotecan, were evaluated in this retrospective study (patient database from SmithKline Beecham, Germany). Most of the patients had more than 2 previous courses of chemotherapy. The starting dose was between 1.0 and 1.5 mg/m2 topotecan administered for 5 days every 3 weeks as an i.v. infusion. All patients were evaluated for toxicity, 32 patients for response. RESULTS: The 33 patients received 343 courses of topotecan, an average of more than 10 courses per patient. The highest number of courses given to a single patient was 33. The hematotoxicity was in the expected range, but toxicity was not cumulative. The number of interventions for growth factors and blood cell transfusions were constant over the whole therapy. Dose reductions were conducted in more than 75% of the patients as early as in course two. There was no grade 3 or 4 non-hematological toxicity. Alopecia was the only toxicity to be cumulative. Remissions were observed in 12 out of 32 eligible patients. The remissions were achieved after an average of 4.3 courses (range 2-7). The median time to progression was 33 weeks. CONCLUSION: Long-term therapy with topotecan is reasonable and can be conducted without cumulative hematological toxicity.
UI - 11848523
AU - Gadducci A; Conte P; Cianci C; Negri S; Genazzani AR
TI - Treatment options in patients with recurrent ovarian cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3557-64
AD - Department of Procreative Medicine, Pisa, Italy. firstname.lastname@example.org
The majority of patients with advanced ovarian cancer need a second-line treatment for recurrent disease after surgical cytoreduction and first-line chemotherapy. In these patients, treatment planning is mainly dependent on the platinum-free-interval. The patients may be distinguished as platinum-refractory (progression under platinum-based therapy), platinum-resistant (relapse within 6 months), or platinum-sensitive (relapse after 6 months). Patients with platinum-refractory or -resistant disease should be encouraged to enter clinical trials. Alternatively, these patients could receive tamoxifen or a non-platinum single-agent therapy. Since response rate and duration to different single-agents are similar, patient convenience, toxicities from prior treatment, side-effects and costs play a role in the drug selection for salvage chemotherapy. Patients with platinum-sensitive disease should receive carboplatin based or carboplatin-plus paclitaxel-based regimens. Secondary surgical cytoreduction may have a role in highly selected patients with good performance status, with long disease-free interval and without extra-abdominal or liver metastases.
UI - 11848547
AU - Peters-Engl C; Medl M; Denison U; Sevelda P; Leodolter S; Petru E
TI - Does long-term application of granulocyte colony-stimulating factor adversely influence overall survival in patients with ovarian cancer? A clinical study.
SO - Anticancer Res 2001 Sep-Oct;21(5):3701-6
AD - Department of Gynecology and Obstetrics, Lainz Medical Center, Vienna, Austria.
The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.
UI - 11603001
AU - Meredith RF; Alvarez RD; Partridge EE; Khazaeli MB; Lin CY; Macey DJ;
TI - Austin JM Jr; Kilgore LC; Grizzle WE; Schlom J; LoBuglio AF Intraperitoneal radioimmunochemotherapy of ovarian cancer: a phase I study.
SO - Cancer Biother Radiopharm 2001 Aug;16(4):305-15
AD - Department of Radiation Oncology, University of Alabama at Birmingham, Comprehensive Cancer Center, Wallace Tumor Institute-117, 1530 3rd Avenue South, Birmingham, AL 35294-6832, USA. email@example.com
A phase I trial was designed to examine the feasibility of combining interferon and Taxol with intraperitoneal radioimmunotherapy (177Lu-CC49). Patients with recurrent or persistent ovarian cancer confined to the abdominal cavity after first line therapy, Karnofsky performance status > 60, adequate liver, renal and hematologic function, and tumor that reacted with CC49 antibody were enrolled. Human recombinant alpha interferon (IFN) was administered as 4 subcutaneous injections of 3 x 10(6) U on alternate days beginning 5 days before RIT to increase the expression of the tumor-associated antigen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m2 compared to 177Lu-CC49 alone (45 mCi/m2). Taxol, which has radiosensitizing effects as well as antitumor activity against ovarian cancer, was given intraperitoneally (i.p.) 48 hrs before RIT. It was initiated at 25 mg/m2 and escalated at 25 mg/m2 increments to 100 mg/m2. Subsequent groups of patients were treated with IFN + 100 mg/m2 Taxol + escalating doses of 177Lu-CC49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for 177Lu-CC49 was 40 mCi/m2 when given with IFN + 100 mg/m2 Taxol. Interferon increased the effective whole body half-time of radioactivity and the whole body radiation dose. Taxol did not have a significant effect on pharmacokinetic or dosimetry parameters. Four of 17 patients with CT measurable disease had a partial response (PR) and 4 of 27 patients with non-measurable disease have progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m2) with RIT using 177Lu-CC49 and interferon was well tolerated, with bone marrow suppression as the dose-limiting toxicity.
UI - 11772280
AU - Harries M; Kaye SB
TI - Recent advances in the treatment of epithelial ovarian cancer.
SO - Expert Opin Investig Drugs 2001 Sep;10(9):1715-24
AD - CRC Department of Medical Oncology, The Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK. firstname.lastname@example.org
Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with the overall 5-year survival being just 30%. The majority of patients with this disease will require treatment with cytotoxic chemotherapy. It is now well established that the platinum agents (cisplatin or carboplatin) are the most important drugs to be included in first-line regimens. More recently, randomised trials have confirmed the benefit of the addition of taxanes to platinum-containing regimens and the standard of care has become the combination of carboplatin and paclitaxel. Several unanswered questions remain regarding the optimal schedule, the optimum duration of treatment, possible benefits to be gained from the addition of other drugs and whether paclitaxel the best taxane. Despite high response rates to first line chemotherapy, the majority of patients with advanced ovarian cancer will relapse and will be candidates for further chemotherapy, which can palliate symptoms and improve survival even in recurrent disease. For a patient relapsing within six months of first-line treatment, studies have shown that there is little point in rechallenge with the same drugs. However, for patients who have a longer treatment-free interval the response rates to rechallenge with platinum is significant. A number of drugs have been shown to have activity in platinum- and taxane-refractory disease and are approved for this and/or other applications. These include topotecan, etoposide, pegylated liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxaliplatin and vinorelbine. Anti-oestrogens such as tamoxifen have a small but significant response rate. Recurrent ovarian cancer is a good setting to test investigational agents and compounds with promising activity including new platinums and taxoids, as well as a range of new compounds. Non-cytotoxic approaches that are showing promise include therapies designed to overcome drug resistance, signal transduction inhibitors, immunotherapy and gene therapy.
UI - 11857347
AU - Vikhanskaya F; Falugi C; Valente P; Russo P
TI - Human papillomavirus type 16 E6-enhanced susceptibility to apoptosis induced by TNF in A2780 human ovarian cancer cell line.
SO - Int J Cancer 2002 Feb 20;97(6):732-9
AD - Molecular Pathology Section, Laboratory of Experimental Oncology, National Institute for Research on Cancer, Genoa, Italy.
In our study, we show that expression of HPV-16 E6 sensitizes TNF-induced cytotoxicity of human ovarian cancer cell line A2780. This effect is not related to a different number of TNF receptors present on cell membrane. The major induction of massive apoptosis induced by TNF is not p53- and p21(waf-1)-dependent but it is principally related to NF-kappaB inhibition in A2780/E6 cells. Consistently to NF-kappaB inhibition a rapidly release of cytochrome c and severe induction of DNA fragmentation are seen in A2780/E6 cells. Also in human colon cancer cell line HCT-116/E6 the expression of HPV-16 E6 enhances TNF-cytotoxicity. This effect is not present in the HCT-116/mu-p53 clone (transfected with a dominant-negative mutated p53 transgene). Thus, taken together all these observations suggest that HPV-16 E6 sensitizes A2780 and HCT-116 cells to TNF; this effect is not p53-dependent, but it is essentially mediated through an inhibition in activating NF-kappaB activities. Copyright 2001 Wiley-Liss, Inc.
UI - 11760646
AU - Lehoczky O; Bagameri A; Udvary J; Pulay T
TI - [Second-line chemotherapy with paclitaxel for ovarian cancer]
SO - Orv Hetil 2001 Oct 21;142(42):2299-301
AD - Nogyogyaszati Onkologiai Osztaly, Orszagos Onkologiai Intezet, Budapest. email@example.com
The authors summerize the results of second-line combination chemotherapy with paclitaxel (175 mg/m2, 3h) and carboplatin (AUC 5 mg/ml.min) in patients with recurrent epithelial ovarian cancer. The paclitaxel/carboplatin therapy was applied in 57 patients in 297 courses (median course/patient was 5, range 2, 12). Complete response (CR) was found in 3 patients (3/57 = 5%), however the tumorous process progressed after some time. The median progression free interval (PFI) was found to be 15 (range 3,130) weeks, with an average of 24.3 +/- 26.5 weeks. The authors conclude, that second-line paclitaxel combination therapy produces poorer results than the first-line treatment. These results, which are similar to the literature data have led to the agreement: paclitaxel can be applied in ovarian cancer patients only in first-line chemotherapy in Hungary from the year 2000.
UI - 11844842
AU - Abramson N; Stokes PK; Luke M; Marks AR; Harris JM
TI - Ovarian and papillary-serous peritoneal carcinoma: pilot study with thalidomide.
SO - J Clin Oncol 2002 Feb 15;20(4):1147-9
UI - 11847508
AU - Takeuchi T; Suzuki h h; Hayashi u u; Shinagawa T; Araki T
TI - Primary ovarian tumor undergoing surgical management during pregnancy.
SO - J Nippon Med Sch 2002 Feb;69(1):39-42
AD - Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
The aim of this study was to evaluate the preoperative symptoms of patients with primary ovarian tumors undergoing surgery during pregnancy and non-pregnancy. We retrospectively analyzed the medical records of 71 pregnant patients who underwent surgery for primary ovarian tumors (pregnant) and 580 non-pregnant patients (non-pregnant) aged 15similar44 years old. In the non-pregnant group, 79.7% of the patients complained of abdominal pain at the first examination. However, in the pregnant group, 62.0% of the patients reported no symptoms and 31.0% of them reported abdominal pain (p<0.05). There were no significant differences in the percentage of ovarian malignancies between the two groups (8.5% vs. 6.6%). However, the incidence of the advanced stage of greater-than-or-equal Ic in ovarian malignancies in the non-pregnant group was 42.1%, while it was 0% (p<0.05) in the pregnant group. Ovarian tumors including ovarian malignancies were significantly more frequently diagnosed with no symptoms in the pregnant group than in the non-pregnant group.
UI - 11855871
AU - Gonzalez-Martin A; Crespo C; Garcia-Lopez JL; Pedraza M; Garrido P;
TI - Lastra E; Moyano A Ifosfamide and vinorelbine in advanced platinum-resistant ovarian cancer: excessive toxicity with a potentially active regimen.
SO - Gynecol Oncol 2002 Mar;84(3):368-73
AD - Medical Oncology Service, Alcala de Henares University, Madrid, 28034, Spain. firstname.lastname@example.org
OBJECTIVES: The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer. PATIENTS AND METHODS: Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed. CONCLUSION: This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.
UI - 11890098
AU - Kim RY
TI - Recent advances in the treatment of gynecologic malignancies: an overview of the GOG phase III trials.
SO - Gan To Kagaku Ryoho 2002 Feb;29 Suppl 1():125-40
AD - Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
UI - 11751481
AU - Menon C; Kutney SN; Lehr SC; Hendren SK; Busch TM; Hahn SM; Fraker DL
TI - Vascularity and uptake of photosensitizer in small human tumor nodules: implications for intraperitoneal photodynamic therapy.
SO - Clin Cancer Res 2001 Dec;7(12):3904-11
AD - Harrison Department of Surgical Research, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.
PURPOSE: i.p. spread of cancers is a common clinical problem, with limited treatment options leading to morbidity and death. i.p. photodynamic therapy (IP-PDT) combines maximal surgical debulking of gross tumor with intraoperative light delivery to the peritoneum after preoperative i.v. injection of photosensitizer to treat residual disease. An issue of concern in IP-PDT is the potential lack of photosensitizer uptake by residual small tumor nodules (STNs) < or =5 mm in maximum diameter and by microscopic residual disease caused by incomplete development of a vascular supply. This study examined the existence of vasculature and Photofrin (PF) uptake in STNs in 12 patients in a Phase II clinical trial for IP-PDT. EXPERIMENTAL DESIGN: Patients received PF 2.5 mg/kg i.v. 48 h before surgery. STNs obtained during surgery were cryosectioned, immunostained for platelet/endothelial cell adhesion molecule 1, and analyzed by light microscopy. Mean vascular densities in STNs were determined by counting microvessels within a x200 field (0.28 mm(2) area). Sections were also examined for PF uptake by fluorescence image analysis using an epifluorescence microscope and IPLab Spectrum software. RESULTS: Data obtained showed that tumors as small as 1 mm in diameter stained positive for platelet/endothelial cell adhesion molecule 1 and contained PF. A negative control from a patient not given PF showed no detectable fluorescence. The average of all mean vascular densities in STNs was determined to be 100 +/- 29. CONCLUSIONS: We conclude that STNs, as small as 1 mm in diameter, have a functional vasculature, because these tumors show PF uptake after i.v. delivery. Both properties are crucial for the treatment of residual STNs by IP-PDT after surgical debulking.
UI - 11589365
AU - Li QQ; Ding L; Reed E
TI - Proteasome inhibition suppresses cisplatin-dependent ERCC-1 mRNA expression in human ovarian tumor cells.
SO - Res Commun Mol Pathol Pharmacol 2000 May-Jun;107(5-6):387-96
AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. email@example.com
One of the major problems with ovarian cancer treatment is the clinical development of resistance to cisplatin. Considerable efforts have been directed toward the identification of biological and pharmacological agents that would reverse drug resistance to cisplatin. ALLnL is an inhibitor of the proteasome that can inhibit the ubiquitin-proteasome pathway, which plays an essential role in many processes in cell life. We have recently shown that ALLnL, at concentrations that do not appear harmful, has significantly enhanced DNA platination and decreased DNA repair of cisplatin-DNA adducts in human A2780/CP70 ovarian carcinoma cells. These activities of proteasome inhibition were also associated with substantially increased cisplatin toxicity in these cells. In this communication, we demonstrate that treatment of A2780/CP70 cells with ALLnL blocks cisplatin-induced ERCC-1 mRNA expression in a concentration- and time-dependent manner, as measured by Northern blot analysis. In addition, we showed that the cisplatin-dependent increase in steady-state levels of ERCC-1 mRNA was prevented by pretreatment with lactacystin, a potent and specific inhibitor of proteasome. These results suggest that the effect of proteasome inhibition on cisplatin cytotoxicity, DNA platination, and DNA repair of cisplatin adducts in ovarian cancer cells may be through down-regulating ERCC-1 expression.
UI - 11821450
AU - Barakat RR; Sabbatini P; Bhaskaran D; Revzin M; Smith A; Venkatraman E;
TI - Aghajanian C; Hensley M; Soignet S; Brown C; Soslow R; Markman M; Hoskins WJ; Spriggs D Intraperitoneal chemotherapy for ovarian carcinoma: results of long-term follow-up.
SO - J Clin Oncol 2002 Feb 1;20(3):694-8
AD - Gynecology Service, Department of Surgery, Gynecology Disease Management Team, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. firstname.lastname@example.org
PURPOSE: To determine long-term survival and predictors of recurrence in a retrospective cohort of patients with epithelial ovarian cancer treated with intraperitoneal (IP) chemotherapy. PATIENTS AND METHODS: Records were reviewed of 433 patients who received IP therapy for ovarian cancer between 1984 and 1998; follow-up data were available for 411 patients. IP therapy was provided as consolidation therapy (n = 89), or for treatment of persistent (n = 310) or recurrent (n = 12) disease after surgery and initial systemic therapy; therapy usually consisted of platinum-based combination therapy. Statistical analysis included tests for associations between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox proportional hazard model. RESULTS: The mean age of patients was 52 years (range, 25 to 76 years). Distribution by stage and grade was as follows: stage I, 7; II, 24; III, 342; IV, 52; not available (NA), 8; and grade 1, 30; 2, 99; and 3, 289; NA, 15. The median survival from initiation of IP therapy by residual disease was none, 8.7 years; microscopic, 4.8 years; less than 1 cm, 3.3 years; more than 1 cm, 1.2 years. In a multivariate analysis, the only significant predictors of long-term survival were grade and size of residual disease at initiation of IP therapy. CONCLUSION: Prolonged survival was observed in selected patients receiving IP platinum-based therapy. It is not possible to determine the contribution of IP therapy to survival in this study. A relationship between size of disease at the initiation of IP therapy and long-term survival was demonstrated.
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