Pancreatic cancer – gemcitabine + other drugs but not oxaliplatin – pro

Lay Summary: Gemcitabine is a standard drug for pancreatic cancer. Combining it with other drugs may make it work better but that is not yet completely clear.

Locally advanced and metastatic pancreatic adenocarcinomas carry a very poor prognosis. In patients treated with the standard palliative treatment gemcitabine (GEM), median survival still remains only 6 months. Over the last several years, many trials have been designed combining GEM with various other drugs to treat chemo-naive patients, with the aim to improve overall survival. Unfortunately, none of the GEM-based combinations studied so far have reached that objective, with the exception of GEM plus Erlotinib, which showed a slight increase in OS to 6.4 months. However, some trials – mainly those using platinum based combinations – have shown an increase in response rate and time to progression. Some supportive evidence is available also for Taxotere/gemcitabine, the regimen used in this case.

The EORTC-GI Group compared a regimen of Taxotere® and Gemzar® to a regimen of Taxetore® and Platinol® for the treatment of advanced or metastatic (80%) pancreatic cancer.  This was a randomized trial, with 49 patients receiving Taxotere® and Gemzar® and 47 receiving Taxotere® and Platinol®. Six cycles of treatment were administered to 44% of patients, with 29% receiving more than 6 cycles. The Gemzar®/Taxotere® arm was associated with low platelets and edema, while the Taxotere®/Platinol® arm had more neutropenia. The response rate was 15.8% for the Gemzar®/Taxotere® arm and 16.1% for the Taxotere®/Platinol® arm. The median survival was 7.4 months for Gemzar®/Taxotere® and 6.3 months for the Taxotere®/Platinol®. There were 11 patients alive in the Gemzar®/Taxotere® arm and 9 in the Taxotere®/Platinol® arm. They concluded that the Gemzar®/Taxotere® arm had more manageable toxicity and possibly better activity. They will be performing a randomized phase III trial to confirm these results.

The Hoosier Oncology Group evaluated a regimen of Gemzar® and Taxotere®.  The response rate was 24%, with a median duration of response of 16 weeks. Thirty-five percent of patients had stable disease. The one-year survival was 27.3% and toxicity appeared to be acceptable.

German researchers also evaluated the combination of Gemzar® and Taxotere® for the treatment of patients with advanced pancreatic cancer. They observed a 24% response rate, with 3% (one patient) achieving a CR. The median survival was 9 months and toxicity was mild to moderate.

These results are not impressive and NCCN does not list this regimen.

Researchers from Austria evaluated the effects of Gemzar® with or without Xeloda® in 83 patients with metastatic pancreatic cancer. 3 Forty-two patients received bi-weekly Gemzar® (2200 mg per square meter as a 30 min. infusion) and 41 patients received the same GemzarÒ dose and schedule plus oral Xeloda® at a dose of 2500 mg per square meter from days 1 to 7. The PR rate was 14 % for the Gemzar® alone group and 17% for the Gemzar® plus Xeloda® group. Stable disease was observed in 43% of Gemzar® alone patients and 56% of the combined group. Median survival was 4 months for the Gemzar® group and 5.1 months for the Xeloda® group, with overall survivals of 8.2 and 9.5 months, respectively. Using a clinical benefit scale, there was clinical benefit for 33% of patients receiving Gemzar® alone and 48.3% for those receiving Gemzar® and Xeloda®. The toxicities of the two regimens appeared to be equivalent and these investigators were enthusiastic about this drug combination. However, there was no improvement in objective or subjective response. It was speculated that the number of patients studied was too small, possibly the dosage was suboptimal and possibly these agents are not really additive or synergistic.NCCN lists gemcitabien and fluoropyrimidine.

It is natural to put all three drugs together and this triple drug combination is being investigated in a phase II trial.


Practice guideline -

Lutz MP, Ducreux M, Wagener T, et al, Docetaxel/gemcitabine or docetaxel/cisplatin in advanced pancreatic carcinoma: a randomized phase II study of the EORTC-GI group. Proceedings of the American Society of Clinical Oncology 2002;21:125a, abstract 498

Scheithauer W, Schüll B, Ulrich-Pur H, et al, Gemcitabine alone or in combination with capecitabine in patients with advanced pancreatic adenocarcinoma. Proceedings of the American Society of Clinical Oncology;21:126a, abstract number 500, pancreatic

Moore MJ; Goldstein D; Hamm J; Figer A; Hecht JR; Gallinger S; Au HJ; Murawa P; Walde D; Wolff RA; Campos D; Lim R; Ding K; Clark G; Voskoglou-Nomikos T; Ptasynski M; Parulekar W
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical
J Clin Oncol. 2007 May 20;25(15):1960-6.

Schneider BP, Ganjoo KN, Seitz DE, et al, Phase II study of gemcitabine and docetaxel in combination for advanced pancreatic cancer – a Hoosier Oncology Group study. Proceedings of the American Society of Clinical Oncology 2002; 21:137a, abstract number 546

Schmidt C, Fahlke J, Kettner E, et al, Phase II multicenter study of gemcitabine and docetaxel in patients with inoperable or metastatic pancreatic cancer. Proceedings of the American Society of Clinical Oncology 2002;21:145a, abstract number 577.

V. Heinemann, R. Labianca, A. Hinke, and C. Louvet
Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study
Ann. Onc., October 1, 2007; 18(10): 1652 – 1659.

D. H. Palmer, D. D. Stocken, H. Hewitt, C. E. Markham, A. B. Hassan, P. J. Johnson, J. A. C. Buckels, and S. R. Bramhall
A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin
Ann. Surg. Oncol., July 1, 2007; 14(7): 2088 – 2096.

NCCN, Pancreatic PNAC-G, 1 2016

T. Seufferlein, J.B. Bachet, E. Van Cutsem, P. Rougier and on behalf of the ESMO Guidelines W, Pancreatic adenocarcinoma: ESMOESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2012) 23 (suppl 7): vii33-vii40

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