A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer.
Cancer Chemother Pharmacol
; 70(6): 875-81, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-23053263
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 ANDMETHODS:
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/m(2), gemcitabine 750 mg/m(2), and capecitabine 750 mg/m(2) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Adenocarcinoma
/
Antineoplastic Combined Chemotherapy Protocols
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Cancer Chemother Pharmacol
Year:
2012
Type:
Article
Affiliation country:
United States