A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma

Abstract

Conventional chemotherapy for unresectable or metastatic adenocarcinoma of the pancreas has had little effect on palliation or survival. Almost all studies of systemic therapy have involved empiric use of a variety of Phase II or conventional agents alone or in combination. On the basis of recent studies using a human tumor pancreatic cancer (PC) xenograft in nude mice, a Phase I clinical trial of cisplatin, high‐dose cytosine arabinoside (Ara‐C), and caffeine (CAC) was performed in patients with advanced incurable PC. A tolerable dose and schedule of the three agents were developed. Seven of 18 patients with measurable disease in this Phase I trial had partial responses to CAC. A Phase III comparison of CAC versus standard treatment using streptozotocin, mitomycin, and 5‐fluorouracil (SMF) was performed. Eighty‐two patients with advanced PC were entered into this random assignment trial. The two treatment arms were well balanced for the usual prognostic factors. Although the acute (e.g., nausea and vomiting) toxicities of CAC were greater than those of SMF, both groups of patients tolerated treatment reasonably well. Ninety percent of patients were evaluable for response. Two patients (5.5%) on the CAC treatment arm (95% confidence interval [CI], 0% to 15%) and four patients (10.2%) on the SMF treatment arm (95% CI, 1% to 22%) had objective responses (partial response in measurable disease or improvement in evaluable disease). No complete remissions were observed. The 95% confidence limits of response for CAC and SMF overlapped. The median duration of survival for all patients on the SMF treatment arm was 10 months, although it was 5 months on the CAC treatment arm (P = 0.008). In this Phase III comparison, CAC was not superior to conventional therapy with SMF in terms of response and was inferior for survival. Neither regimen is effective treatment for advanced PC.

Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models

“…Although the clinical investigation of several antitumour agents has been conducted with a principal focus on fluorouracil, no agent has been found to suppress tumour growth. Also, there is no obvious improvement in the results of treatment with multiple drug therapy (Kelsen et al, 1991;Topham et al, 1991;Rougier et al, 1993;Nose et al, 1999) or the biochemical modulation of fluorouracil (Pazdur et al, 1992;Louvet et al, 1993;Weinerman and MacCormick, 1994;Bernhard et al, 1995). Gemcitabine, a nucleoside analogue, is efficacious in relieving the symptoms such as algia or general state in the case of nonscaling down of tumours (Casper et al, 1994).…”

Randomized trials in exocrine pancreatic cancer

“…Zastosowanie streptozotocyny wraz z 5-FU nie przedłużyło czasu przeżycia tak, aby zrównoważyć toksyczność i większe koszty terapii [93,94]. Dwa niewielkie badania nad połączeniem 5-FU ze streptozotocyną i mitomycyną C dały dość obiecujące wyniki, lecz obejmowały one zbyt krótki czas obserwacji [95,96]. Leczenie fluorouracylem z cyklofosfamidem, metotreksatem i winkrystyną wzbudziło spore zainteresowanie w 1980 i 1990 r., lecz od tego czasu nie podjęto dalszych badań [97,98].…”

Advances in the treatment of patients with pancreatic cancer: improvement in symptoms and survival time

“…This has recently been reviewed by Moore (1994). A myriad of combination regimens have been assembled and tested (Frey et al, 1981;Horton et al, 1981;Bukowski et al, 1983;Cullinan et al, 1985Cullinan et al, , 1991GITSG, 1986;Oster et al, 1986;Kelsen et al, 1991;Moore, 1994). Once again, there is no evidence from these studies that combination chemotherapy is superior to therapy with 5-FU.…”

“…Once again, there is no evidence from these studies that combination chemotherapy is superior to therapy with 5-FU. The median survival of patients receiving single-agent 5-FU or 5-FU in combination with agents such as doxorubicin, mitomycin C, cisplatin, streptozotocin or others, is 4 months (range 1.8-10 months) (Frey et al, 1981;Horton et al, 1981;Bukowski et al, 1983;Cullinan et al, 1985Cullinan et al, , 1990GITSG, 1986;Oster et al, 1986;Kelsen et al, 1991;Moore, 1994).…”