Chemotherapy for pancreatic carcinoma

Abstract

BACKGROUND Pancreatic cancer is an aggressive disease and its patients typically have a short survival, usually marked by pain and rapid debilitation. The disease has been considered relatively chemoresistant, although many chemotherapy regimens have been described. METHODS Clinical results with chemotherapy, since the first publication of response in 1960, were reviewed for efficacy and toxicity. Emphasis was given to prospective trials with adequate power and clear evaluation criteria and end‐points. RESULTS Published response rates vary enormously in this disease, with rates in earlier single‐institution trials tending to be much higher than those in studies with stringent response criteria, particularly recent cooperative group trials. Using stringent criteria, the upper limit of the objective response rate is approximately 20%. No convincing improvement in median survival can yet be attributed to chemotherapy. Few trials have measured quality of life, but symptomatic palliation rates may exceed objective response rates. Some low‐toxicity regimens (such as those based on infusional 5‐FU) yield response rates as high as some more toxic combinations. CONCLUSIONS Many early trials significantly overstate the efficacy of chemotherapy for patients with pancreatic cancer, apparently due to flexibility of response criteria. However, useful symptomatic palliation may occur even without an objective partial response. It is possible that slow resolution of the desmoplastic component of these tumors may underestimate tumor killing. Thus, quality of life is an important parallel endpoint (with survival and response) in chemotherapy trials in this disease. Cancer 1996;78:654‐63.

Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450

“…4 Even if resection can be undertaken, recurrence at the original site of the tumour shortens survival. 5,6 Despite recent developments, 7,8 conventional chemotherapy, using drugs such as cisplatin, 5-fluorouracil, taxol and more recently gemcitabine, has had limited success in the clinic since the necessary high local drug doses cannot be achieved without significant systemic toxicity. 3,5,8 Novel chemotherapeutic prodrugs might offer a way round these toxicity problems if they could be activated locally.…”

Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine

“…In all, 80 -95% of patients are inoperable at diagnosis and only about 1% of patients are still alive 5 years from the time of diagnosis (Ahlgren, 1996). Gemcitabine (2 0 ,2 0 difluorodeoxycytidine), a nucleoside analogue with a mild toxicity profile (Aapro et al, 1998), has been shown to improve both clinical benefit and survival in patients with advanced pancreatic cancer compared to treatment with 5-fluorouracil, although overall survival was poor with a median survival of less than 6 months (Burris et al, 1997).…”

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma

“…Third, from our small trial it remains unclear as to whether the survival length of our patients achieving SD is due to the specific antitumour treatment or might have been achieved with best supportive care alone. Whereas the superiority of a specific antitumour treatment over best supportive care has been demonstrated for other highly aggressive tumours (Ahlgren, 1996;Scheithauer et al, 1999;Hoffman and Glimelius, 1998;Burris et al, 1997), meta-analyses from randomized trials using doxorubicin for HCC did not reveal any survival benefit (Mathurin et al, 1998;Simonetti et al, 1997). However, these data were generated from the treatment with the free drug doxorubicin.…”