Alternating Gemcitabine/Nab-Paclitaxel (GA) and 5-FU/Leucovorin/Irinotecan (FOLFIRI) as First-Line Treatment for De Novo Metastatic Pancreatic Cancer (MPC): Safety and Effect

Simple Summary This study explores the efficacy and safety of alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) regimens in patients with metastatic pancreatic cancer (MPC). The approach aims to reduce toxicity, slow resistant cancer biology, and facilitate the incorporation of other therapeutic agents. The results show a median overall survival (mOS) of 13.2 months, competitive with standard regimens, and encouraging long-term survival rates at 18 and 24 months. The toxicity profile is favorable, and supportive growth factors were not needed. This regimen appears promising for MPC and warrants further investigation.Abstract Background: Both gemcitabine- and 5-fluorouracil (5-FU)-based chemotherapy regimens have demonstrated efficacy in metastatic pancreatic cancer (MPC). Alternating these regimens may reduce toxicity, slow resistant cancer biology emergence, and provide a platform for the addition of other therapeutic agents. Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) in MPC has previously been reported at our own institution and elsewhere. An extension of our institutional observations is reported here. Methods: Patient eligibility required the following: biopsy-proven de novo MPC, no prior evidence of disease on CT, ECOG performance status (PS) <= 2, and bi-dimensionally measurable disease. Treatment (Tx) entailed gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 1, (8), 15 alternating every 8 weeks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 weeks. Tx spanned up to 12 cycles. Tx thereafter was decided following patient/physician discussion. Results: Median overall survival (mOS) was 13.2 months (95% CI 10.9-16.5 months). Median progression-free survival (mPFS) was 8.5 months (95% CI, 7.1-9.9). The 6-, 12-, 18-, and 24-month OS rates were 88%, 54%, 36%, and 20%, respectively. The disease control rate at 16 weeks was 83% (37% PR, 46% SD). Hematologic toxicity grade >= 3 included 9.3% anemia, 10.2% neutropenia, and 4.6% thrombocytopenia. Neutrophil growth factors were not used in this cohort. Non-hematologic toxicities grade >= 3 included neuropathy 0.9%, nausea/vomiting 0.9%, and diarrhea 0.9%. No patients experienced mucositis on this regimen. Conclusions: Alternating GA/FOLFIRI in MPC has a favorable toxicity profile in comparison to current standard regimens. Median OS was at least competitive with standard regimens, and longer-term (18 and 24 months) OS seemed particularly encouraging. Treatment for >= 48 weeks and ECOG PS of zero at the time of treatment initiation were prognostically significant. Further investigation using this regimen including randomized comparisons, the incorporation of molecular data, and use of additional agents is merited.

Automated summary

This study investigates the effectiveness and safety of alternating gemcitabine/nab-paclitaxel and 5-FU/leucovorin/irinotecan regimens in patients with metastatic pancreatic cancer. The results show competitive median overall survival rates and encouraging long-term survival rates. This regimen has potential for the treatment of metastatic pancreatic cancer.