ACOSG ZO531: Report on a Multicenter, Phase II Trial for Adjuvant Therapy of Resected Pancreatic Cancer Using Cisplatin, 5-FU, and Alpha-Interferon
Surgery is considered the only curative therapy for pancreatic cancer. However, 50-80% of patients will develop recurrence after surgery. For this reason, patients also receive adjuvant (meaning postoperative) chemotherapy, either with or without radiation therapy. While this therapy improves survival, it only results in a 10-20% 5- year survival. Previous studies have shown that the addition of interferon alpha may make cisplatin chemotherapy work better in making tissues sensitive to radiation (radiosensitizing) and in improving survival.
This study gave all participants 5-FU, cisplatin, and alpha interferon. The study hoped to enroll 93 patients, but was stopped early with 89 participants due to high rates of toxicities. Overall survival (OS) was 69% at 20 months and 58% at 2 years. 96% of patients had a grade 3 or 4 (on a scale of 0-4, 4 being the most severe). The toxicities most commonly seen were anorexia (loss of appetite), dehydration, diarrhea and nausea. These toxicities were significant, but manageable with supportive care.
There are now three studies evaluating the efficacy of cisplatin, 5-FU, alpha interferon, and radiation. These studies include the Virginia Mason study (Picozzi V.J. et al., ACSO Annual Meeting 2003), the CapRI study (Knaebel H.P. et al., BMC Cancer, 2005; presently under analysis), and the present study. Data is available for over 174 patients from these studies, and they have consistently demonstrated a 2-year OS of greater than 50%. The CapRI study is the only randomized trial, and results are pending. It is important to note that the patients in this study were highly selected, and there is the potential for bias regarding patient enrollment.
The greatest problem with this regimen is the toxicity related to treatment, as seen now in multiple studies. The majority of these toxicities were related to anorexia and dehydration. It is unclear what supportive care patients received, such as whether feeding tubes were placed and used, the use of IV fluids, monitoring of patient weight during treatment, and use of pre-albumin levels. Without this information, it is difficult to know if there was adequate supportive care to get patients safely through treatment. The inability to complete treatment was associated with worse outcome and this was likely affected by the high toxicity associated with treatment. However, despite this toxicity and the significant number of patients who could not complete therapy, the outcomes were quite good compared with historical controls. Hence, if the tolerability of this treatment could be improved, such as through better supportive care, outcomes might improve as well.