A phase I study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Marisa E Hill, Xiaobai Li, Sharon Kim, Angela Campbell, Kristy Culler, Mark Bloomston, Mark Zalupski, Gwen Hejna, Tanios Bekaii-Saab
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 67 Issue 3 Pg. 511-7 (Mar 2011) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20461379 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CA-19-9 Antigen
• Taxoids
• Deoxycytidine
• Docetaxel
• Capecitabine
• Fluorouracil
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, pathology)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• CA-19-9 Antigen (metabolism)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Docetaxel
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Prospective Studies
• Survival
• Taxoids (administration & dosage)
• Gemcitabine