Lay Summary: There is little evidence that treating with chemo after initial chemo fails is beneficial.
Patients with advanced pancreatic cancer profit from palliative chemotherapy but the role of second-line chemotherapy is not yet established. Pancreatic cancer affects more than 30,000 people in the United States each year and when the cancer does not respond to standard chemotherapy, additional treatments have not been approved. Research on effectiveness of second line therapy is ongoing; so far it appears that selected patients can benefit form second line chemotherapy but the best regimens and how to select patients has not been determined.
The evidence for second-line chemotherapy after progression on a gemcitabine-based regimen is scant. The CONKO-003 investigators randomly assigned patients in the second line of chemotherapy to either a regimen of 5-FU, leucovorin, and oxaliplatin (OFF regimen) or best supportive care (BSC). The OFF regimen consisted of folinic acid (200 mg/m2) followed by 5-FU (2 g/m2 [24 hours] on days 1, 8, 15, and 22) and oxaliplatin (85 mg/m2 on days 8 and 22). After a rest of 3 weeks, the next cycle was started on day 43. The trial was terminated early because of poor accrual, and only 46 patients were randomly assigned to either the OFF regimen or BSC. Median second-line survival was 4.82 months (95% CI, 4.29–5.35) for the OFF-regimen treatment and 2.30 months (95% CI, 1.76–2.83) with BSC alone (HR, 0.45; 95% CI, 0.24–0.83). Median OS was 9.09 months for the sequence of gemcitabine/5-FU, leucovorin, and oxaliplatin or GEM-OFF and 7.90 months for gemcitabine/best supportive care or GEM-BSC. The early closure of the study and the very small number of patients made the P values misleading. Therefore, second-line chemotherapy with the OFF regimen may be associated with improved survival but requires more study.
NCCN recommends capecitabine, Folfox or CapeOx)XelOx) for second line therapy on p. PANC-G.
Pelzer U, Schwaner I, Stieler J, et al.: Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 47 (11): 1676-81, 2011
A. Mancuso, P. Saletti, S. Sacchetta, E. Romagnani, F. Cavalli and C. N. Sternberg Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 14107
T. Herrmann, D. Jaeger, W. Stremmel, C. Herrmann
Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis.Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 15187