Gemcitabine plus nab-paclitaxel for advanced pancreatic cancer after first-line FOLFIRINOX: single institution retrospective review of efficacy and toxicity

Yue Zhang, Howard Hochster, Stacey Stein, Jill Lacy, Yue Zhang, Howard Hochster, Stacey Stein, Jill Lacy

Abstract

Background: We conducted a retrospective review of the dose, toxicity, and efficacy of second line gemcitabine plus nab-paclitaxel (G + Nab-P) after FOLFIRINOX in patients with metastatic and locally advanced unresectable pancreatic cancer.

Methods: In this retrospective study, we included all patients with locally advanced unresectable or metastatic pancreatic cancer who were treated at Yale Cancer Center with G + Nab-P between 12/2011 and 12/2013 after receiving first line FOLFIRINOX. For each patient, demographics, prior therapy, doses of G + Nab-P (cumulative doses and dose intensity relative to full dose G + Nab-P), hematologic toxicities, best response by RECIST, time to treatment failure (TTF), and survival were compiled. Median TTF and overall survival (OS) were calculated by Kaplan-Meier method.

Results: 28 patients were treated with G + Nab-P after first line FOLFIRINOX. The median TTF was 12.0 weeks (range 2.0-36.0), and the median OS was 23.0 weeks (range 2.1-85.4). Five patients had a partial response (response rate 17.9 %), and 28.6 % of patients had stable disease for ≥7 weeks. A decline in CA 19-9 and CEA by >30 % was observed in 13 (46.4 %) and 11 (39.3 %) patients, respectively. The median relative dose intensities were 62.4 and 57.5 % for G and Nab-P, respectively. Grade ≥3 hematologic toxicities included neutropenia in 17.9 %, anemia in 25.0 %, and thrombocytopenia in 25.0 % of patients.

Conclusions: Second line G + Nab-P following FOLFIRINOX is feasible, and demonstrated modest activity and clinical benefit in advanced pancreatic cancer. The optimum sequencing and dosing of these active regimens warrants further evaluation in prospective trials.

Keywords: FOLFIRINOX; Gemcitabine plus nab-paclitaxel; Pancreatic cancer; Second line treatment.

References

    1. Niederhuber JE, Brennan MF, Menck HR. The National Cancer Data Base report on pancreatic cancer. Cancer. 1995;76(9):1671–1677. doi: 10.1002/1097-0142(19951101)76:9<1671::AID-CNCR2820760926>;2-R.
    1. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol Off J Am Soc Clin Oncol. 1997;15(6):2403–2413.
    1. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825. doi: 10.1056/NEJMoa1011923.
    1. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703. doi: 10.1056/NEJMoa1304369.
    1. Berger AK, Weber TF, Jager D, Springfeld C. Successful treatment with nab-paclitaxel and gemcitabine after FOLFIRINOX failure in a patient with metastasized pancreatic adenocarcinoma. Onkologie. 2013;36(12):763–765.
    1. Portal A, Pernot S, Siauve N, Landi B, Lepere C, Colussi O, et al. Sustained response with gemcitabine plus nab-paclitaxel after folfirinox failure in metastatic pancreatic cancer: report of an effective new strategy. Clin Res Hepatol Gastroenterol. 2014;38(2):e23–e26. doi: 10.1016/j.clinre.2014.01.005.
    1. Salem ME, Alistar AT, Dyson G, Stanski N, Mahaseth H, Choi M, et al. Albumin-bound paclitaxel plus gemcitabine after first-line FOLFIRINOX therapy in patients with pancreatic cancer. ASCO Meet Abstr. 2014;32(15 suppl):e15252.
    1. Bertocchi P, Abeni C, Meriggi F, Rota L, Rizzi A, Di Biasi B, et al. Gemcitabine plus nab-paclitaxel as second-line and beyond treatment for metastatic pancreatic cancer: a single institution retrospective analysis. Rev Recent Clin Trials. 2015;10(2):142–5. doi: 10.2174/1574887110666150417115303.
    1. Pelzer U, Schwaner I, Stieler J, Adler M, Seraphin J, Dorken B, 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 (Oxford, England: 1990) 2011;47(11):1676–1681. doi: 10.1016/j.ejca.2011.04.011.
    1. Pelzer U, Stieler J, Roll L, Hilbig A, Dorken B, Riess H, et al. Second-line therapy in refractory pancreatic cancer. Results of a phase II study. Onkologie. 2009;32(3):99–102. doi: 10.1159/000197769.
    1. Dahan L, Bonnetain F, Ychou M, Mitry E, Gasmi M, Raoul JL, et al. Combination 5-fluorouracil, folinic acid and cisplatin (LV5FU2-CDDP) followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301) Gut. 2010;59(11):1527–1534. doi: 10.1136/gut.2010.216135.
    1. Novarino A, Satolli MA, Chiappino I, Giacobino A, Bellone G, Rahimi F, et al. Oxaliplatin, 5-fluorouracil, and leucovorin as second-line treatment for advanced pancreatic cancer. Am J Clin Oncol. 2009;32(1):44–48. doi: 10.1097/COC.0b013e31817be5a9.
    1. Ulrich-Pur H, Raderer M, Verena Kornek G, Schull B, Schmid K, Haider K, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer. 2003;88(8):1180–1184. doi: 10.1038/sj.bjc.6600883.
    1. Hosein PJ, de Lima Lopes G, Jr, Pastorini VH, Gomez C, Macintyre J, Zayas G, et al. A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol. 2013;36(2):151–156. doi: 10.1097/COC.0b013e3182436e8c.
    1. Xenidis N, Chelis L, Amarantidis K, Chamalidou E, Dimopoulos P, Courcoutsakis N, et al. Docetaxel plus gemcitabine in combination with capecitabine as treatment for inoperable pancreatic cancer: a phase II study. Cancer Chemother Pharmacol. 2012;69(2):477–484. doi: 10.1007/s00280-011-1717-6.
    1. Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(30):4787–4792. doi: 10.1200/JCO.2007.11.8521.
    1. Rahma OE, Duffy A, Liewehr DJ, Steinberg SM, Greten TF. Second-line treatment in advanced pancreatic cancer: a comprehensive analysis of published clinical trials. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2013;24(8):1972–1979. doi: 10.1093/annonc/mdt166.
    1. Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, et al. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009;101(10):1658–1663. doi: 10.1038/sj.bjc.6605374.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere