Gemcitabine, paclitaxel, and radiation for locally advanced pancreatic cancer: a Phase I trial.
OBJECTIVE
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of gemcitabine, paclitaxel, and concurrent radiation for pancreatic cancer.


METHODS
Twenty patients with locally unresectable pancreatic cancer were studied. The initial dose level was gemcitabine 75 mg/m(2) and paclitaxel 40 mg/m(2) weekly for 6 weeks. Concurrent radiation to 50.4 Gy was delivered in 1.8 Gy fractions. The radiation fields included the primary tumor, plus the regional peripancreatic, celiac, and porta hepatis lymph nodes.


RESULTS
Dose-limiting toxicities of diarrhea, dehydration, nausea, and anorexia occurred in 3 of 3 patients at the second dose level of gemcitabine, 150 mg/m(2)/week. An intermediate dose level of gemcitabine, 110 mg/m(2)/week, was added, but gastrointestinal toxicity and pulmonary pneumonitis were encountered. The MTD therefore was gemcitabine 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and concurrent radiation. Two of 11 patients treated at the MTD had Grade 3/4 toxicity. Four of 10 assessable patients treated at the MTD responded (40%), including one pathologic complete response.


CONCLUSIONS
The maximum tolerated dosage of gemcitabine is 75 mg/m(2)/week with paclitaxel 40 mg/m(2)/week and conventional 50.4 Gy radiation fields. A Phase II Radiation Therapy Oncology Group study is under way.
The Brown University Oncology Group, Department of Medicine, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA. hsafran@lifespan.org
Howard
H
Safran
Thomas
T
Dipetrillo
David
D
Iannitti
Daniel
D
Quirk
Paul
P
Akerman
Dennis
D
Cruff
William
W
Cioffi
Samir
S
Shah
Nadia
N
Ramdin
Tyvin
T
Rich
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000628:therapy*; D000093542:Gemcitabine
D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine