A phase I study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas
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- Hill, M.E., Li, X., Kim, S. et al. Cancer Chemother Pharmacol (2011) 67: 511. doi:10.1007/s00280-010-1348-3
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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.