Abstract
In 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/m2, fluorouracil 500 mg/m2,epi-doxorubicin 35 mg/m2, 6S-steroisomer of leucovorin 250 mg/m2and glutathione 1.5 g/m2. On the other days filgrastim 5 μg kg–1was administered by subcutanous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m2every 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. © 2001 Cancer Research Campaign http://www.bjcancer.com
Keywords: gastric cancer, sequential chemotherapy, docetaxel
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- Cascinu S., Labianca R., Alessandroni P., Marcellini M., Silva R. R., Pancera G., Testa E., Martignoni G., Barni S., Frontini L. Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer. J Clin Oncol. 1997 Nov;15(11):3313–3319. doi: 10.1200/JCO.1997.15.11.3313. [DOI] [PubMed] [Google Scholar]
- Cascinu S., Labianca R., Graziano F., Pancera G., Barni S., Frontini L., Luporini G., Cellerino R., Catalano G. Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Br J Cancer. 1998 Aug;78(3):390–393. doi: 10.1038/bjc.1998.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cortes J. E., Pazdur R. Docetaxel. J Clin Oncol. 1995 Oct;13(10):2643–2655. doi: 10.1200/JCO.1995.13.10.2643. [DOI] [PubMed] [Google Scholar]
- Day R. S. Treatment sequencing, asymmetry, and uncertainty: protocol strategies for combination chemotherapy. Cancer Res. 1986 Aug;46(8):3876–3885. [PubMed] [Google Scholar]
- Findlay M., Cunningham D., Norman A., Mansi J., Nicolson M., Hickish T., Nicolson V., Nash A., Sacks N., Ford H. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609–616. doi: 10.1093/oxfordjournals.annonc.a058932. [DOI] [PubMed] [Google Scholar]
- Fizazi K., Zelek L. Is òne cycle every three or four weeks' obsolete? A critical review of dose-dense chemotherapy in solid neoplasms. Ann Oncol. 2000 Feb;11(2):133–149. doi: 10.1023/a:1008344014518. [DOI] [PubMed] [Google Scholar]
- Hill M. E., Cunningham D. Medical management of advanced gastric cancer. Cancer Treat Rev. 1998 Apr;24(2):113–118. doi: 10.1016/s0305-7372(98)90077-9. [DOI] [PubMed] [Google Scholar]
- Kelsen D. P. Adjuvant and neoadjuvant therapy for gastric cancer. Semin Oncol. 1996 Jun;23(3):379–389. [PubMed] [Google Scholar]
- Melcher A. A., Mort D., Maughan T. S. Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) as neoadjuvant chemotherapy in gastro-oesophageal cancer. Br J Cancer. 1996 Nov;74(10):1651–1654. doi: 10.1038/bjc.1996.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Pronk L. C., Stoter G., Verweij J. Docetaxel (Taxotere): single agent activity, development of combination treatment and reducing side-effects. Cancer Treat Rev. 1995 Sep;21(5):463–478. doi: 10.1016/0305-7372(95)90030-6. [DOI] [PubMed] [Google Scholar]
- Roth A. D., Maibach R., Martinelli G., Fazio N., Aapro M. S., Pagani O., Morant R., Borner M. M., Herrmann R., Honegger H. Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO). Ann Oncol. 2000 Mar;11(3):301–306. doi: 10.1023/a:1008342013224. [DOI] [PubMed] [Google Scholar]
- Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1–10. doi: 10.1016/0197-2456(89)90015-9. [DOI] [PubMed] [Google Scholar]
- Sulkes A., Smyth J., Sessa C., Dirix L. Y., Vermorken J. B., Kaye S., Wanders J., Franklin H., LeBail N., Verweij J. Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group. Br J Cancer. 1994 Aug;70(2):380–383. doi: 10.1038/bjc.1994.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Webb A., Cunningham D., Scarffe J. H., Harper P., Norman A., Joffe J. K., Hughes M., Mansi J., Findlay M., Hill A. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261–267. doi: 10.1200/JCO.1997.15.1.261. [DOI] [PubMed] [Google Scholar]