A phase I study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas
- 101 Downloads
Pancreas cancer remains a formidable challenge. We report the first prospective analysis of the 3-drug combination of gemcitabine (G), docetaxel (T) and capecitabine (X) (mGTX) with schedule modification to maximize biomodulation of X.
We conducted a dose escalation study of mGTX in first-line treatment of metastatic pancreas cancer using three dose levels (DL 1-3). Patients received docetaxel on days 1 and 8, gemcitabine on days 8 and 15, and capecitabine on days 8 through 21. Gemcitabine dose was fixed at 750 mg/m2 over 75 min, capecitabine was given twice daily and escalated from 500 to 650 mg/m2 at DL2 and docetaxel increased from 30 to 36 mg/m2 at DL3.
Twenty-one patients (18 evaluable) were enrolled in the study. MTD was reached at DL3 and one DLT was observed at DL2 (prolonged neutropenia). The most common grade 3/4 toxicities were leukopenia (29%) and neutropenia (29%) and fatigue (25%). Tumor growth control rate was 80% (11% PR; 69% SD lasting at least 3 months). Median progression-free-survival was 5.8 months (95% CI 2.7, 10.6) and median overall survival was 7.4 months (95% CI 3.8 16.8). CA 19-9 decreased by at least 50% from baseline in half the patients.
mGTX demonstrates acceptable tolerability with interesting activity in patients with pancreatic cancer. The recommended doses for phase II studies are docetaxel 36 mg/m2 days 1 and 8, gemcitabine 750 mg/m2 over 75 min days 8 and 15, and capecitabine 625 mg/m2 twice daily days 8 through 21.
KeywordsPancreas Adenocarcinoma Gemcitabine Capecitabine Docetaxel
This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Roche Laboratories Inc.
Conflict of interest statement
Tanios Bekaii-Saab has received Research Grants from Sanofi-Aventis and Roche, is on the speaker bureau for Sanofi-Aventis and Lilly and has received honoraria from Sanofi-Aventis and Lilly. Other Co-Authors have no declared conflict of interest.
- 2.Burris HA III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15(6):2403–2413PubMedGoogle Scholar
- 3.Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Ding K, Ptaszynski M, Parulekar W (2005) Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). In: Proceedings of ASCO 2005Google Scholar
- 9.Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27(33):5513–5518CrossRefPubMedGoogle Scholar
- 13.Nadell P, Shapiro C, Otterson GA, Hauger M, Erdal S, Kraut E, Clinton S, Shah M, Stanek M, Monk P, Villalona-Calero MA (2002) Pharmacobiologically based scheduling of capecitabine and docetaxel results in antitumor activity in resistant human malignancies. J Clin Oncol 20(11):2616–2623CrossRefGoogle Scholar
- 15.Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, Lenzi R, Abbruzzese J (2003) Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21(18):3402–3408CrossRefPubMedGoogle Scholar
- 16.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216CrossRefPubMedGoogle Scholar
- 17.Stathopoulos GP, Syrigos K, Polyzos A, Fountzilas G, Rigatos SK, Ziras N, Potamiannou A, Tsiakopoulos I, Androulakis N, Aravantinos G, Athanasiadis A, Papakotoulas P, Georgoulias V (2004) Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study. Ann Oncol 15(2):224–229CrossRefPubMedGoogle Scholar
- 18.Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer S, Tàmas K, Kornek V, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W (2007) Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25(16):2212–2217CrossRefPubMedGoogle Scholar
- 20.Allendorf JD, Lauerman M, Bill A, DiGiorgi M, Goetz N, Vakiani E, Remotti H, Schrope B, Sherman W, Hall M, Fine RL, Chabot JA (2008) Neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic adenocarcinoma: feasibility, efficacy, and survival. J Gastrointest Surg 12(1):91–100CrossRefPubMedGoogle Scholar