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A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer

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Abstract

Background

Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma.

Materials and methods

Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0–1 were eligible to participate. Study design utilized a 3 + 3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1–7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3–4 hematologic toxicities and grade 2–4 hand–foot syndrome, neuropathy, or diarrhea.

Results

Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100 mg/m2, gemcitabine 750 mg/m2, and capecitabine 750 mg/m2 twice daily. Patients received a median of four treatment cycles (range 1–16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand–foot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7 %) experienced at least one grade 3–4 adverse event. Grade 3–4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3 %) exhibited a partial response, and 6 of 12 patients (50 %) with elevated CA19–9 at baseline had a ≥50 % biomarker decline.

Conclusion

While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens.

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Conflict of interest

Dr. Andrew H. Ko received research funding from Celgene to help support the conduct of this investigator-initiated clinical trial.

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Authors and Affiliations

  1. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero Street, Box 1705, San Francisco, CA, 94115, USA

    Andrew H. Ko, Thach-Giao Truong, Emily Kantoff, Kimberly A. Jones, Elizabeth Dito, Anna Ong & Margaret A. Tempero

  2. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Kimberly A. Jones

Authors
  1. Andrew H. Ko
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  2. Thach-Giao Truong
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  3. Emily Kantoff
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  4. Kimberly A. Jones
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  5. Elizabeth Dito
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  6. Anna Ong
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  7. Margaret A. Tempero
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Correspondence to Andrew H. Ko.

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Ko, A.H., Truong, TG., Kantoff, E. et al. A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Cancer Chemother Pharmacol 70, 875–881 (2012). https://doi.org/10.1007/s00280-012-1979-7

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  • DOI: https://doi.org/10.1007/s00280-012-1979-7

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