A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer

Abstract

SummaryIn advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m 2 , fluorouracil 500 mg/m 2 ,epidoxorubicin 35 mg/m 2 , 6S-steroisomer of leucovorin 250 mg/m 2 and glutathione 1.5 g/m 2 . On the other days filgrastim 5 µg kg -1 was administered by subcutanous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m 2 every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

“…The overall response rate of 56% was within the range (30 -70%) of previous major protocols such as FAMTX, ELF, EAP, ECF, and recent taxane-based (Bokemeyer et al, 1997;Kollmannsberger et al, 2000;Cascinu et al, 2001) or irinotecan-based regimens (Bleiberg, 1999;Ajani et al, 2002;Slater et al, 2002). Recently, three other studies, using different administrating schedules of oxaliplatin and 5-FU, have also demonstrated a good efficacy in gastric cancer (Louvet et al, 2002;Kim et al, 2003;Al-Batran et al, 2004).…”

Docetaxel, 5-fluorouracil, and leucovorin as treatment for advanced gastric cancer: results of a phase II study

“…This same combination plus 5-FU shows similar activity [16]. In addition, a recent phase II trial considering the sequential application of docetaxel after PELF showed major objective responses, with manageable toxicity [17].…”

Randomised, non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial

“…There is clear evidence that docetaxel has non-cross-resistant activity in advanced oesophagogastric cancer. Docetaxel has efficacy as a single agent after failure of platinum and fluoropyrimidines, as well as additive activity when used in combination with cisplatin and 5-FU (Cascinu et al, 2001;Van Cutsem et al, 2006). However, significant myelosuppression with 3-weekly administration poses a major problem for the development of combination chemotherapy regimens, because the myelosuppressive effects add to the toxicities of other chemotherapy agents.…”