Treatment Pathways for Carcinoma of the Pancreas Metastatic

Treatment Pathways for Carcinoma of the Pancreas Metastatic Unresectable, not metastatic Resectable

Treatment Pathways for Carcinoma of the Pancreas Metastatic cancer

GTX Chemotherapy for Pancreatic Cancer Robert L Fine, William Sherman, John Chabot, Stephen Schreibman, Michael Williams, Michael Cusnir, David Van Echo, Columbia Universirty, College of Physicians and Surgeons, New York, NY; University of Virginia, Charlottesville, VA; University of Maryland, Baltimore, MD.

Hypothesis PC cells frequently have ras and p 53 mutations that block certain apoptosis pathways. Chemotherapy drugs should be screened in vitro against cell lines with ras and p 53 mutations.

In vitro findings: There is synergism between 5 -FU and gemcitabine and between gemcitabine and taxotere. Synergism between gemcitabine and taxotere was observed at nanomolar concentrations of taxotere.

In Vitro Schedule-dependent Interaction between Docetaxel and Gemcitabine in Human Gastric Cancer Cell Lines Luca Ricotti, Anna Tesei, Franca De Paola, Paola Ulivi, Giovanni Luca Frassineti, Carlo Milandri, Dino Amadori and Wainer Zoli Clinical Cancer Research Vol. 9, 900 -905, February 2003 Doc + Gem Dox Gem

GTX Xeloda 1500 – 2000 mg/m 2/day in 2 daily doses, Day 1 – 14 Gemcitabine 750 - 1000 mg/m 2 i. v. over 2 hours, Day 4, 11 Taxotere 30 mg/m 2 i. v. Day 4, 11 Fine, Sherman, et al. ASCO 2002, p 144 a, abstract #575

GTX 24 patients with metastatic tumor: PR 50% SD 25% NR 25% Fine, Sherman, et al. ASCO 2002, p 144 a, abstract #575

Other protocols for metastatic carcinoma of the pancreas Cis-platinum + irinotecan Cis-platinum + gemcitabine

Treatment Pathways for Carcinoma of the Pancreas Unresectable, not metastatic

Downstaging patients with locally advanced, non-metastatic tumor 8 patients with locally advanced tumor treated with GTX -> Radiation + weekly Gemcitabine -> Surgery: 5 had Whipple with negative margins and normal post-op CA 19 -9 Fine, Sherman, et al. ASCO 2002, p 144 a, abstract #575

Treatment Pathways for Carcinoma of the Pancreas S/p resection, no known residual or metastatic tumor

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma External beam radiation 4, 500 c. Gy to 5, 400 c. Gy, 25 fractions in 5 weeks Cis-platinum 30 mg/m 2 once a week 5 -FU 200 mg/m 2/day continuous i. v. infusion a-interferon 3 x 106 u sq every other day Followed by continuous i. v. 5 -FU weeks 9 14 and 17 22 Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367 -71

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma Between 1993 and 1998 33 patients at VMMC, Seattle WA had adjuvant therapy with or a) “GITSG” bolus 5 -FU and radiation b) “IFN based” chemoradiation Not a randomized trial Comparable stage and prognostic factors in both groups Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367 -71

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367 -71

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma 26 month median follow-up: 2 -year survival GITSG style 54% IFN-based 84% Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367 -71

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma Audit and update by committee from ACOS: 53 patients treated at VMMC analyzed with adjuvant “Ifn-based” chemoradiation and 5 -FU after Whipple 49% 5 -year survival

Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma 70% required treatment delay 43% required hospitalization 90% received full dose of radiation 85% received full dose of chemotherapy

ACOSOG Z 5031 - Phase II Study Eligibility: R 0 or R 1 resection T 1 - T 3, N 0 - N 1, M 0 Adenocarcinoma of head of pancreas Changes in treatment compared to VMMC study: 175 mg/m 2/day 5 -FU instead of 200 mg/m 2/day 5040 c. Gy in 28 fractions - 180 c. Gy fractions instead of 200 c. Gy fractions