A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma

Derek Shek, Jeff Longmate, David I. Quinn, Kim A. Margolin, Przemyslaw Twardowski, David R Gandara, Paul Frankel, Chong-Xian Pan, Primo N Lara

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: This study was conducted to evaluate the efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with pegylated-IFNα (PEG-IFNα) in patients with advanced renal cell carcinoma. Methods: Progression-free survival (PFS) rate at 6 months >50% was considered promising for further evaluation. Patients with unresectable or metastatic disease, unlimited prior therapies, and adequate performance status and endorgan function were eligible. PEG-IFNα was dosed subcutaneously once weekly (initially 6 μg/kg/week, later reduced to 4 μg/kg/week) for 12 weeks. Gefitinib was given 250 mg orally once daily until progression or intolerance. Results: Twenty-one patients were accrued. Fourteen patients had a prior nephrectomy, and twelve had prior systemic therapy. The 6-month PFS was 29% (95%CI 15-56%). Best responses by RECIST criteria: complete, partial (1, plus 3 unconfirmed) stable (Uhlman et al. Clin Cancer Res 1:913-920, 1995), and progression (Sirotnak et al. Clin Cancer Res 6:4885-4892, 2000). Response duration: complete response (35+ months) and partial response (2, 3, 3, 37 months). Median PFS and overall survival were 5.3 (95%CI 3-10.1) and 13.6 (95%CI 10.3-NA) months, respectively. Most common toxicities included myelosuppression, rash, and nausea. Conclusions: Although generally well tolerated, gefitinib plus PEG-IFNα did not meet the pre-specified 6-month PFS rate >50%. Further evaluation of similar regimens would require appropriate molecular selection of subjects most likely to benefit. Thus, preclinical studies to determine candidate predictive markers for this combination are warranted.

Original languageEnglish (US)
Pages (from-to)494-499
Number of pages6
JournalInternational Journal of Clinical Oncology
Volume16
Issue number5
DOIs
StatePublished - Oct 2011

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Renal Cell Carcinoma
Disease-Free Survival
Survival Rate
Exanthema
Nephrectomy
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Nausea
Patient Selection
Neoplasms
Survival
gefitinib
Therapeutics

Keywords

  • Cytokine therapy
  • Epidermal growth factor receptor (EGFR) inhibitor
  • Renal cell cancer

ASJC Scopus subject areas

  • Oncology
  • Surgery
  • Hematology
  • Medicine(all)

Cite this

A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma. / Shek, Derek; Longmate, Jeff; Quinn, David I.; Margolin, Kim A.; Twardowski, Przemyslaw; Gandara, David R; Frankel, Paul; Pan, Chong-Xian; Lara, Primo N.

In: International Journal of Clinical Oncology, Vol. 16, No. 5, 10.2011, p. 494-499.

Research output: Contribution to journalArticle

Shek, Derek ; Longmate, Jeff ; Quinn, David I. ; Margolin, Kim A. ; Twardowski, Przemyslaw ; Gandara, David R ; Frankel, Paul ; Pan, Chong-Xian ; Lara, Primo N. / A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma. In: International Journal of Clinical Oncology. 2011 ; Vol. 16, No. 5. pp. 494-499.
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abstract = "Background: This study was conducted to evaluate the efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with pegylated-IFNα (PEG-IFNα) in patients with advanced renal cell carcinoma. Methods: Progression-free survival (PFS) rate at 6 months >50{\%} was considered promising for further evaluation. Patients with unresectable or metastatic disease, unlimited prior therapies, and adequate performance status and endorgan function were eligible. PEG-IFNα was dosed subcutaneously once weekly (initially 6 μg/kg/week, later reduced to 4 μg/kg/week) for 12 weeks. Gefitinib was given 250 mg orally once daily until progression or intolerance. Results: Twenty-one patients were accrued. Fourteen patients had a prior nephrectomy, and twelve had prior systemic therapy. The 6-month PFS was 29{\%} (95{\%}CI 15-56{\%}). Best responses by RECIST criteria: complete, partial (1, plus 3 unconfirmed) stable (Uhlman et al. Clin Cancer Res 1:913-920, 1995), and progression (Sirotnak et al. Clin Cancer Res 6:4885-4892, 2000). Response duration: complete response (35+ months) and partial response (2, 3, 3, 37 months). Median PFS and overall survival were 5.3 (95{\%}CI 3-10.1) and 13.6 (95{\%}CI 10.3-NA) months, respectively. Most common toxicities included myelosuppression, rash, and nausea. Conclusions: Although generally well tolerated, gefitinib plus PEG-IFNα did not meet the pre-specified 6-month PFS rate >50{\%}. Further evaluation of similar regimens would require appropriate molecular selection of subjects most likely to benefit. Thus, preclinical studies to determine candidate predictive markers for this combination are warranted.",
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AU - Shek, Derek

AU - Longmate, Jeff

AU - Quinn, David I.

AU - Margolin, Kim A.

AU - Twardowski, Przemyslaw

AU - Gandara, David R

AU - Frankel, Paul

AU - Pan, Chong-Xian

AU - Lara, Primo N

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AB - Background: This study was conducted to evaluate the efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with pegylated-IFNα (PEG-IFNα) in patients with advanced renal cell carcinoma. Methods: Progression-free survival (PFS) rate at 6 months >50% was considered promising for further evaluation. Patients with unresectable or metastatic disease, unlimited prior therapies, and adequate performance status and endorgan function were eligible. PEG-IFNα was dosed subcutaneously once weekly (initially 6 μg/kg/week, later reduced to 4 μg/kg/week) for 12 weeks. Gefitinib was given 250 mg orally once daily until progression or intolerance. Results: Twenty-one patients were accrued. Fourteen patients had a prior nephrectomy, and twelve had prior systemic therapy. The 6-month PFS was 29% (95%CI 15-56%). Best responses by RECIST criteria: complete, partial (1, plus 3 unconfirmed) stable (Uhlman et al. Clin Cancer Res 1:913-920, 1995), and progression (Sirotnak et al. Clin Cancer Res 6:4885-4892, 2000). Response duration: complete response (35+ months) and partial response (2, 3, 3, 37 months). Median PFS and overall survival were 5.3 (95%CI 3-10.1) and 13.6 (95%CI 10.3-NA) months, respectively. Most common toxicities included myelosuppression, rash, and nausea. Conclusions: Although generally well tolerated, gefitinib plus PEG-IFNα did not meet the pre-specified 6-month PFS rate >50%. Further evaluation of similar regimens would require appropriate molecular selection of subjects most likely to benefit. Thus, preclinical studies to determine candidate predictive markers for this combination are warranted.

KW - Cytokine therapy

KW - Epidermal growth factor receptor (EGFR) inhibitor

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