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

Abstract

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m À2 (day 1) (arm A); docetaxel 75 mg m À2 (day 8) and gemcitabine 1250 mg m À2 (days 1,8) (arm B) or docetaxel 25 mg m À2 and gemcitabine 800 mg m À2 (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P ¼ 0.102, P ¼ 0.056, P ¼ 0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5 -20.6); arm B 18.1 months (95% CI: 15.9 -20.3); arm C, 13.7 months (95% CI: 12.8 -14.6). Neutropenia was the predominant grade 3 -4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P ¼ 0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

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).…”

Severe pulmonary toxicity in patients with leiomyosarcoma after treatment with gemcitabine and docetaxel

“…Our results show that G/D therapy has a serious risk of pulmonary toxicity in line with others [4][5][6]. Possibly, gemcitabine-induced cytokine release can potentiate the lung toxicity of docetaxel, however, docetaxel might also augment gemcitabine-induced cytokine release.…”

Phase II study of carboplatin followed by sequential gemcitabine and paclitaxel as first-line treatment for advanced ovarian cancer

“…There was no pulmonary toxicity in this study in contrast to the experience of Harries et al (25) with a similar protocol but with paclitaxel on days 1, 8, and 15 during which several patients experienced breathlessness, interstitial lung changes, and decreased diffusing capacity [DLCO (diffusion capacity of the lung for carbon monoxide)]. Vasey et al (26) also reported significant pulmonary toxicity with a similar study of carboplatin followed by docetaxel and gemcitabine on days 1, 8, and 15. The weekly schedule appears to be related to pulmonary toxicity and should be avoided.…”