A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer

Abstract

Summary Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m2 iv.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-') starting on al., 1984;Dhingra et al., 1985; Kawahara et al., 1991). Treatment regimens in which one further active chemotherapeutic agent has been added to vinca alkaloid and cisplatin have been tried in an attempt to improve response and survival rates. The combination of mitomycin with VP (MVP) has been reported to achieve response rates of 20-61% (Kris et al., 1986; Einhorn et al., 1986; Miller et al., 1986; Joss et al., 1990;Fukuoka et al., 1991). Although these intensive combination chemotherapy regimens achieve an improvement in objective response, serious drug-related toxicity is often experienced. Active chemotherapeutic regimens that are less toxic would therefore be desirable.Although 5-fluorouracil (5-FU) shows limited activity as a single agent in NSCLC, it reacts synergistically with CDDP against murine tumours (Schabel et al., 1979; Mabel and Little, 1979). This has prompted clinical studies of the combination of CDDP and 5-FU against NSCLC. Weiden et al. (1985) have reported a response rate of 37% in NSCLC using this combination. Continuous infusion (CI) of 5-FU has been found to increase the therapeutic response and decrease myelosuppression compared with the use of bolus injections (Seifert et al., 1975;Kish et al., 1985). Decker et al. (1983) found the combination of CDDP and a 5 day infusion of 5-FU useful in the treatment of head and neck cancers. They reported a 94% response rate, including a complete response rate of 63%. In a pilot study by the Mid-Atlantic Oncology Program, CDDP (120 mg m-2) infused over 24 h + CI 5-FU gave a response rate of 47% in advanced NSCLC (Heim et al., 1986). Toxicology profiles of these CDDP + 5-FU regimens indicate less haematological and nephrological toxicity than standard dose VP and MVP regimens. However, a higher incidence of severe mucositis was observed, and, if doxorubicin was also included, clinically significant myelosuppression, similar to that encountered with VP and MVP regimens, was also experienced (Ruckdeschel et al., 1981). Although improved response rates have been achieved, an optimum dose and schedule has yet to be identified.These reports encouraged us to perform a phase II trial of CDDP and VDS in combination with CI 5-FU against advanced NSCLC. We decided to administer VP separately from CI 5-FU, in an attempt to minimise toxicity without affecting efficacy. In most of the earlier studies CDDP and 5-FU were administered on the same day. The trial was designed so that CDDP + VDS and CI 5-FU were injected on alternate weeks. The immediate objectives were to determine the major objective response rate to this treatment programme, and to define the toxicities involved. The activity of this combination against advanced NSCLC has not been studied previously.Patients a...

An Open-Label, Multicenter, Three-Stage, Phase II Study of S-1 in Combination with Cisplatin as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer

“…5,6 The most recent studies have evaluated bolus infusions of 5-FU, usually in combination with other agents such as cisplatin and etoposide or a vinca alkaloid, or radiotherapy. [7][8][9][10][11] Single agent 5-FU is modestly active in combination with leucovorin, with a 16% objective response rate noted in one study. 9 Although 5-FU may be more active when administered continuously, prolonged infusion is cumbersome for most patients.…”