A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: A Southwest oncology group (SWOG 9924) study (original) (raw)

Abstract

Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with surgically incurable locally advanced or metastatic PC. Between 6/1/2000 and 11/20/2001, 58 cases were accrued, 53 of whom were eligible and analyzable. Patients were required to have a performance status (PS) 0 to 1, be able to take oral medications, and to have adequate renal, hepatic, and hematologic functions. Fifty-five percent were male. Median age was 64.7 years (38.9 to 80.6), and patients had no previous systemic therapy for advanced PC. Treatment consisted of R115777 300 mg po bid given for 3 out of every 4 weeks. Toxicities were as follows: Grade 3 in 19/53 (36%), grade 4 in 53 (173%), and grade 5 in 53 (8%). Most frequent toxicities were: anemia 35/53 (66%), fatigue and malaise 33/53 (62%), nausea 31/53 (58%). Grade 5 toxicities included: thromboembolism 1, infection 2, other 1. Median survival was 2.6 months (mo) (95% CI 2.1–3.6), 6-mo survival is 19% (95% CI, 8–29%), median time to treatment failure was 1.4 mo (95% GI 1.1–1.6). R115777 is ineffective as monotherapy in advanced pancreatic cancer.

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Authors and Affiliations

  1. St. Vincent’s Comprehensive Cancer Center, NY, NY
    John S. Macdonald
  2. Southwest Oncology Group Statistical Center, Seattle, WA
    Sheryl McCoy
  3. University of Texas Medical Branch, Galveston, TX
    Robert P. Whitehead
  4. School of Medicine, University of Southern California, Los Angeles, CA
    Syma Iqbal
  5. Central Illinois Community Clinical Oncology Program, Decatur, IL
    James L. Wade III
  6. Greenville Community Clinical Oncology Program, Greenville, SC
    Jeffrey K. Giguere
  7. MD Anderson Cancer Center, Houston, TX
    James L. Abbruzzese
  8. St. Vincent’s Comprehensive Cancer Center, 325 W 15th Street, New York, NY, 10011
    John S. Macdonald

Authors

  1. John S. Macdonald
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  2. Sheryl McCoy
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  3. Robert P. Whitehead
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  4. Syma Iqbal
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  5. James L. Wade III
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  6. Jeffrey K. Giguere
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  7. James L. Abbruzzese
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Correspondence toJohn S. Macdonald.

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Macdonald, J.S., McCoy, S., Whitehead, R.P. et al. A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: A Southwest oncology group (SWOG 9924) study.Invest New Drugs 23, 485–487 (2005). https://doi.org/10.1007/s10637-005-2908-y

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