A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer

Abstract

Background. With the introduction of cisplatincontaining regimens in the treatment of advanced gastric cancer, promising clinical results have been reported. A 61.5% response rate was observed with a combination of 5‐fluorouracil (5‐FU) infusion and bolus cisplatin; however, the superiority of cisplatin‐containing regimens to other regimens has not been clearly verified in any randomized controlled studies. A prospective, randomized study of 5‐FU and cisplatin (FP) versus 5‐FU, doxorubicin, and mitomycin C (FAM) versus 5‐FU alone (FU) in previously untreated patients with advanced gastric cancer is reported. Methods. A total of 324 patients were entered into the trial and 295 patients (103 for FP, 98 for FAM, 94 for FU) were evaluable. The patients were randomized to receive FP, FAM, or FU after stratifying by the following factors: performance status, presence of measurable disease, and resection of the primary tumor. Results. The overall response rate for patients with measurable disease in the FP arm was significantly higher than in the FAM and FU arms (51% for FP; 25% for FAM; 26% for FU). The durations of response for each arm, however, were not significantly different. Even though the median time to progression for the FP arm (21.8 weeks) was longer than that for the FAM arm (12 weeks; P < 0.05) and for the FU arm (9.1 weeks; P < 0.005), there was no statistical difference in overall survival among the three arms. Toxicity for all three regimens was moderate and consisted primarily of myelosuppression, nausea, vomiting, and alopecia. Conclusions. Although the FP regimen showed a significantly higher response rate and a longer time to progression than the FAM or FU regimens, a survival benefit was not observed.

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients

“…Similarly, alopecia was a rare side effect when compared with anthracyclines or etoposide-based regimens. The efficacy of this FOLFOX treatment was not different from that observed in phase II -III studies with other second-or third-generation polychemotherapy regimens in AGC (Lacave et al, 1991;Wils et al, 1991;Kelsen et al, 1992;Kim et al 1993;Rougier et al, 1994;Vanhoefer et al, 2000). Interestingly, the median TTP and OS observed in our study population are similar to those reported in a prospectively randomised study comparing ECF with the standard regimen FAMTX (Webb et al, 1997).…”

“…In particular, in the study by Louvet et al (2002), in which oxaliplatin was administered at a dose of 100 mg m À2 , peripheral neuropathy was reported in 87% of the treated population and was severe (grade 3 toxicity) in 21% of the patients. In our series, diarrhoea, nausea and vomiting were the most common side effects among nonhaematologic toxicities, but were mild and occurred less frequently when compared with CDDP-based regimens such as FUP and ECF (Kim et al, 1993;Webb et al, 1997). Similarly, alopecia was a rare side effect when compared with anthracyclines or etoposide-based regimens.…”

Combination chemotherapy of irinotecan plus cisplatin for advanced gastric cancer: efficacy and feasibility in clinical practice

“…[2][3][4][5] However, none of the combination regimens have yet demonstrated a prolongation of survival as compared with 5-fluorouracil alone; [6][7][8] accordingly new active chemotherapy regimens are needed. Irinotecan hydrochloride (CPT-11) is a water-soluble, semisynthetic derivative of camptothecin (CPT) that retains the original antitumor activity of CPT, but has lower toxicity.…”

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C

“…Most are triple therapies incorporating 5FU and cisplatin with either epirubicin or paclitaxel. Response rates of 48 -70% have been achieved (Kim et al, 1993;Ilson et al, 1998) with a 2-year survival of 13.5% (Findlay et al, 1994); however, in general, the responses are often short lived and these treatments are associated with varying degrees of toxicity.…”