A phase II feasibility study of carboplatin followed by sequential weekly paclitaxel and gemcitabine as first-line treatment for ovarian cancer

Abstract

A total of 53 women with chemotherapy-naïve stage Ic-IV ovarian cancer were treated with four cycles of carboplatin area under the curve 7 every 3 weeks, followed by four cycles of paclitaxel 70 mg m À2 (days 1, 8, and 15) and gemcitabine 1000 mg m À2 (days 1 and 8) every 3 weeks. In all, 37 (70%) had stage III/IV disease, with 22 (42%) having tumour 42 cm; 38 patients (72%) completed all planned treatment; 27 of the 32 (84%) patients with radiologically evaluable disease had partial or complete responses; and 30 of the 39 patients (77%) with elevated cancer antigen (CA) 125 had a greater than 75% fall in this value. At a median follow-up of 28 months, 31 patients had relapsed with a median progression-free survival of 19.5 months. In total, 79% of patients were alive at 2 years. Common Toxicity Criteria grade 3/4 haematological toxicity, predominantly neutropenia, was seen in 57% of the patients. A certain degree of pulmonary toxicity was observed; eight patients had symptomatic breathlessness, 7 decreased diffusing capacity of the lung for carbon monoxide, and interstitial chest X-ray changes during the weekly phase. In all cases, this toxicity was reversible. No significant neurotoxicity was seen. This regimen is generally well tolerated with encouraging efficacy. However, the observation of pulmonary toxicity, potentially a feature of the weekly taxane -gemcitabine regimen, was of some concern. Alternative schedules, including 3-weekly taxanes, are currently being evaluated.

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel–irinotecan as first-line therapy for ovarian cancer

“…The results, however, are consistent with the 58.7% achieved with carboplatindocetaxel in the SCOTROC I trial on which this study was based (Vasey et al, 2004). Importantly, the median progression-free survival figures of 17.1 and 15.9 months in arms A and B, respectively, are also similar to those previously reported in phase II and III studies of first-line chemotherapy in patients with predominantly stage III -IV EOC (International Collaborative Ovarian Neoplasm Group, 2002;Guppy et al, 2004;Harries et al, 2004;Vasey et al, 2004), providing preliminary evidence that the regimens we tested have efficacy consistent with current first-line therapies. The use of sequential therapy also allowed a preliminary assessment of the relative efficacies of docetaxel and docetaxelirinotecan in improving disease status after single-agent carboplatin.…”

Pulmonary toxicity in patients treated with gemcitabine and a combination of gemcitabine and a taxane: investigation of a signal using postmarketing data

“…We were interested to read a recent article by Vasey et al (2006) in which the authors expressed some concern about the incidence of pulmonary toxicity (Ptox) in patients treated with a taxanegemcitabine regimen, an issue that has been raised by several others (Thomas et al, 2000;Bhatia et al, 2002;Harries et al, 2004). The rare specific adverse drug reactions (ADRs) classified as Ptox are known to occur with the use of gemcitabine (Gem) and both taxanes, docetaxel (Doc) and paclitaxel (Pac).…”

SCOTROC 2A: Carboplatin followed by docetaxel or docetaxel–gemcitabine as first-line chemotherapy for ovarian cancer

“…Importantly, sequential scheduling did not incur loss of efficacy; in these studies, median overall survival ranged from 22 to 30 months (Poole et al, 2000;Tognoni et al, 2000;Guppy et al, 2004). In SCOTROC 2C, the response rate in evaluable patients was 84%, with a median progression-free survival of 19.5 months at a median follow-up of 28 months (Harries et al, 2004). In our study, the response rate of 66% after single-agent carboplatin was improved following sequential treatment with docetaxel-based regimens.…”

“…Lung toxicity has been reported with other weekly taxane -gemcitabine schedules -for example, in the SCOTROC 2C trial, where patients were treated with four cycles of carboplatin followed by weekly paclitaxel -gemcitabine in patients with ovarian cancer (Harries et al, 2004). One trial with paclitaxel plus weekly gemcitabine was discontinued as four out of 12 patients with non-small-cell lung cancer experienced dose- Table 2 Tumour responses after eight cycles of chemotherapy (by treatment arm)…”

“…Preliminary results of the SCOTROC 2B study, which investigated carboplatin followed by docetaxel alone or 3-weekly docetaxel -irinotecan (Jayson et al, 2003), further support this sequential approach and suggest further investigation in ovarian cancer is warranted. Following the results of SCOTROC 2C (Harries et al, 2004), in which pulmonary toxicity was noted with the weekly paclitaxel -gemcitabine schedule, a further feasibility study with the 3-weekly paclitaxel -gemcitabine schedule has also been initiated. We aim to analyse the results of all the SCOTROC 2 trials together (including docetaxel and paclitaxel-based schedules) in order to evaluate the optimal sequence and drug combination for future Phase III testing of a sequential approach to standard, concurrent two-drug chemotherapy administration.…”