Phase II trial of capecitabine and rHu-interferon-α-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity

Ena Segota, Tarek Mekhail, Thomas Olencki, Thomas E. Hutson, Robert Dreicer, Brenda Wacker, Bruno Osterwalder, Paul Elson, Ming Zhou, Ronald M. Bukowski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-α (IFNα), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNα-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted. Patients and Methods: Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m2 twice daily on days 1-14 and 22-36, combined with IFNα-2a 3.0 MU/m2 subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m2 twice daily on days 1-14 and 22-36 in the subsequent 18 patients. Results: Responses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade ≥3 toxicity. Conclusion: The combination of capecitabine and IFNα-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalUrologic Oncology: Seminars and Original Investigations
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2007

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Renal Cell Carcinoma
Interferons
Capecitabine
Thymidine Phosphorylase
Fluorouracil
Histology
Confidence Intervals
Survival

Keywords

  • Cancer
  • Capecitabine
  • Carcinoma
  • Interferon
  • Kidney
  • Renal

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Phase II trial of capecitabine and rHu-interferon-α-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity. / Segota, Ena; Mekhail, Tarek; Olencki, Thomas; Hutson, Thomas E.; Dreicer, Robert; Wacker, Brenda; Osterwalder, Bruno; Elson, Paul; Zhou, Ming; Bukowski, Ronald M.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 25, No. 1, 01.01.2007, p. 46-52.

Research output: Contribution to journalArticle

Segota, Ena ; Mekhail, Tarek ; Olencki, Thomas ; Hutson, Thomas E. ; Dreicer, Robert ; Wacker, Brenda ; Osterwalder, Bruno ; Elson, Paul ; Zhou, Ming ; Bukowski, Ronald M. / Phase II trial of capecitabine and rHu-interferon-α-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity. In: Urologic Oncology: Seminars and Original Investigations. 2007 ; Vol. 25, No. 1. pp. 46-52.
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abstract = "Background: Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-α (IFNα), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNα-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted. Patients and Methods: Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m2 twice daily on days 1-14 and 22-36, combined with IFNα-2a 3.0 MU/m2 subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m2 twice daily on days 1-14 and 22-36 in the subsequent 18 patients. Results: Responses were seen in 4 of 32 patients (12{\%}) (95{\%} confidence interval 4{\%} to 29{\%}), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38{\%}) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63{\%}. Toxicity was moderate to severe and required dose reductions in 88{\%} of patients. There were 23 patients who had grade ≥3 toxicity. Conclusion: The combination of capecitabine and IFNα-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.",
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T1 - Phase II trial of capecitabine and rHu-interferon-α-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity

AU - Segota, Ena

AU - Mekhail, Tarek

AU - Olencki, Thomas

AU - Hutson, Thomas E.

AU - Dreicer, Robert

AU - Wacker, Brenda

AU - Osterwalder, Bruno

AU - Elson, Paul

AU - Zhou, Ming

AU - Bukowski, Ronald M.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Background: Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-α (IFNα), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNα-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted. Patients and Methods: Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m2 twice daily on days 1-14 and 22-36, combined with IFNα-2a 3.0 MU/m2 subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m2 twice daily on days 1-14 and 22-36 in the subsequent 18 patients. Results: Responses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade ≥3 toxicity. Conclusion: The combination of capecitabine and IFNα-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.

AB - Background: Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-α (IFNα), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNα-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted. Patients and Methods: Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m2 twice daily on days 1-14 and 22-36, combined with IFNα-2a 3.0 MU/m2 subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m2 twice daily on days 1-14 and 22-36 in the subsequent 18 patients. Results: Responses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade ≥3 toxicity. Conclusion: The combination of capecitabine and IFNα-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.

KW - Cancer

KW - Capecitabine

KW - Carcinoma

KW - Interferon

KW - Kidney

KW - Renal

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