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

Marisa E. Hill, Xiaobai Li, Sharon Kim, Angela Campbell, Kristy Culler, Mark Bloomston, Mark Zalupski, Gwen Hejna, Tanios Bekaii-Saab

Research output: Contribution to journalArticle

6 Citations (Scopus)

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/m 2 twice daily days 8 through 21.

Original languageEnglish (US)
Pages (from-to)511-517
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Fingerprint

docetaxel
gemcitabine
Pancreas
Adenocarcinoma
Pancreatic Neoplasms
Neutropenia
Leukopenia
Drug Combinations
Disease-Free Survival
Fatigue
Toxicity
Tumors
Appointments and Schedules
Fatigue of materials
Survival
Capecitabine
Growth

Keywords

  • Adenocarcinoma
  • Capecitabine
  • Docetaxel
  • Gemcitabine
  • Pancreas

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

A phase i study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas. / Hill, Marisa E.; Li, Xiaobai; Kim, Sharon; Campbell, Angela; Culler, Kristy; Bloomston, Mark; Zalupski, Mark; Hejna, Gwen; Bekaii-Saab, Tanios.

In: Cancer Chemotherapy and Pharmacology, Vol. 67, No. 3, 01.03.2011, p. 511-517.

Research output: Contribution to journalArticle

Hill, Marisa E. ; Li, Xiaobai ; Kim, Sharon ; Campbell, Angela ; Culler, Kristy ; Bloomston, Mark ; Zalupski, Mark ; Hejna, Gwen ; Bekaii-Saab, Tanios. / A phase i study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 67, No. 3. pp. 511-517.
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AU - Li, Xiaobai

AU - Kim, Sharon

AU - Campbell, Angela

AU - Culler, Kristy

AU - Bloomston, Mark

AU - Zalupski, Mark

AU - Hejna, Gwen

AU - Bekaii-Saab, Tanios

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AB - 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/m 2 twice daily days 8 through 21.

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