A multicenter, phase III randomized trial for stage IIIb/IV NSCLC of weekly paclitaxel and carboplatin vs. standard paclitaxel and carboplatin given every three weeks, followed by weekly paclitaxel
Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 7, 2004
This presentation discusses unapproved dosing schedules for carboplatin and paclitaxel.
C. P. BelaniPresenter's Affiliation:
University of Pittsburg Cancer Institute, Pittsburg, PAType of Session:
- Previous trials evaluating standard three week dosing of paclitaxel and carboplatin in stage IIIb/IV NSCLC have demonstrated response rates of 17-30%, median survival of 7-8 months, one year overall survival of 34-37%, and a 10-17% incidence of Grade III neuropathy.
- An earlier trial of weekly paclitaxel and carboplatin in advanced stage NSCLC demonstrated a median survival of 49 weeks.
- Weekly paclitaxel is administered with ease and well-tolerated by patients.
- This trial was conducted to compare weekly paclitaxel and carboplatin versus standard three week dosing in stage IIIb/IV NSCLC patients.
Materials and Methods
- 444 patients were stratified based on performance status (ECOG 0 or 1 versus 2) and disease stage (IIIb or IV) and then randomized between two arms of the trial.
- Arm 1 (223 pts.) included paclitaxel (100 mg/m2) given on days 1, 8, and 15 and carboplatin (AUC 6) given on day 1. 4 cycles of chemotherapy were administered, and each cycle consisted of 28 days.
- Arm 2 (221 pts.) included paclitaxel (225 mg/m2) and carboplatin (AUC 6) given on day 1. 4 cycles of chemotherapy were administered, and each cycle consisted of 21 days.
- Following initial therapy, patients without evidence of progression received weekly paclitaxel (70 mg/m2) until progression or development of unacceptable toxicity.
- Primary endpoint was overall survival.
- Secondary endpoints included disease progression, objective response rates, and safety profile.
- Patients had pathologically confirmed disease, no history of prior chemotherapy or radiation, and clinically measurable tumor burden.
- The median age of patients was 65 years.
- There were 5% more males on the three week dosing arm and 5% more poor performance status patients on the weekly dosing arm.
- There was no signficant difference in objective response rate (20.3% weekly versus 18.2% standard, p=0.589), duration of response (18.4 wks. weekly versus 17.6 wks. standard, p=0.783), median survival (38.7 wks. weekly versus 44.5 wks. standard, p=0.388), one year survival (39.5% weekly versus 43% standard), and two year survival (19.2% weekly versus 22% standard).
- There was no significant difference in Grade 4 neutropenia (5.1% weekly versus 7.9% standard, p=0.226), Grade 2 neuropathy (p=0.135), Grade 3 neuropathy (p=0.381), or fatigue (4.1% weekly versus 4.7% standard, no p value given).
- The standard dosing arm demonstrated significantly more arthralgia (1.4% weekly versus 5.6% standard, p=0.017), and the weekly dosing arm showed significantly more anemia (8.3% weekly versus 3.3% standard, p=0.026).
- There was no difference in survival between the two dosing regimens.
- The side effect profile between the two groups was comparable, with significantly more arthralgia in the standard arm and significantly more anemia in the weekly arm.
- The weekly paclitaxel maintenance therapy following initial therapy may have improved the overall survival in both groups as compared to previous trials.
Perhaps the most important aspect of this study was the realization of longer overall survival times in both groups as compared to previous trials. This may well be secondary to the maintenance weekly paclitaxel following initial therapy. The two dosing regimens were comparable with respect to response and survival, and the side effect profile was likewise similar. This trial could potentially be used as justification for basing chemotherapy dosing in advanced stage NSCLC on physician and/or patient preference.
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