Gemcitabine, Paclitaxel, and Radiation for Locally Advanced Pancreatic Cancer: A Phase I Trial

Ryan Smith, MD
University of Pennsylvania Cancer Center
Last Modified: November 5, 2001

Presenter: T. Dipetrillo
Presenter's Affiliation: Brown University
Type of Session: Scientific

Background

Locally advanced pancreatic cancer has < 5% 5 year survival despite advances in chemotherapy and radiation advances

Gemcitabine and paclitaxel are both radiation sensitizers

The use of paclitaxel has demonstrated efficacy in RTOG 98-12

The feasibility of concurrent weekly paclitaxel and gemcitabine with radiation is investigated in this phase I study

Materials and Methods

This is a Phase I prospective trial of 20 patients. Sixteen were deemed unresectable by CT +/- ultrasound (via major vessel invasion or extensive adenopathy) and 4 patients had underwent partial resection and had residual disease.

Radiation was delivered at 1.8 Gy/fraction to a dose of 45 Gy to the primary tumor plus regional nodes. Conedown to the primary tumor for an additional 5.4 Gy.

Paclitaxel (40 mg/m2) was delivered weekly

Gemcitabine was given in a dose escalating form: Level I-75 mg/m2/week, Level II-150 mg/m2/week, Level III-110 mg/m2/week)

Dose limiting Toxicity (DLT) was Grade 4 hematologic toxicity or Grade 3 nonhematologic toxicity

Results

Three patients were initially treated with Level I dose (75 mg/m2/wk) with no DLT

Three patients were treated with Level II dose (150 mg/m2/wk), all 3 of which had DLT (GI).

Five patients were treated with Level III dose (110 mg/m2/wk), 3 of which had GI DLT.

Maximally tolerated dose was deemed as 75 mg/m2/wk, and an additonal 8 patients were treated with this dose level. 2/11 had Grade 3/4 toxicity (anorexia/dehydration)

Ten/11 were radiographically evaluable, 4 of which had a PR. These 4 patients had surgery, one of which had a pathological CR. This patient continues to be NED 21 months after surgery.

Author's Conclusions

The maximally tolerated dose was weekly paclitaxel 40 mg/m2/wk, gemcitabine 75 mg/m2/wk and radiation to 50.4 Gy.

Substantial activity was seen with gemcitabine

Enrollment was encouraged into RTOG PA-0020 (paclitaxel, gemcitabine, FTI, radiation to 50.4 Gy)

Clinical/Scientific Implications
Pancreatic cancer has a poor prognosis with standard 5-FU chemotherapy concurrent with radiation. Gemcitabine and paclitaxel have been shown to have significant activity in pancreatic cancer, but (especially gemcitabine) can elicit extensive radiation toxicity. This phase I trial demonstrates the maximally tolerated dose of gemcitabine, allowing further studies to be done. Given that pancreatic cancer has a dismal prognosis with traditional therapies, enrollment onto these studies should be encouraged.

Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology and Pharmacia Oncology.

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