Chemotherapy for renal cell carcinoma – pro

Lay Summary: Chemotherapy is not effective for renal cell carcinoma, although sarcomatoid variants may fare better with chemotherapy.

Chemotherapy in treating renal cell has had a poor record, even though cytotoxic drugs are the cornerstone of therapy for most solid malignancies. Sarcomatoid variants may respond better to chemotherapy but the evidence for this is scant. A comprehensive review of 83 trials involving more than 4,000 patients reported a chemotherapy response rate of 6%.

Historically, patients have shown some response to therapy with the single agents floxuridine, 5-fluorouracil, and vinblastine. Floxuridine and 5-fluorouracil are antimetabolites that work by inhibiting thymidylate synthase, a pivotal enzyme that catalyzes the de novo production of thymidylate and thymidine nucleotides that are necessary for DNA synthesis. Vinblastine binds to tubulin, causing inhibition of the mitosis phase of the cell cycle. A comprehensive review reported overall response rates of 43% or lower in patients receiving floxuridine, an overall response rate of 10% in patients taking 5-fluorouracil, and overall response rates of 7% or lower in patients receiving vinblastine.

More recently, single-agent therapy with capecitabine or gemcitabine has shown some benefit when used in patients with metastatic disease. A phase II study evaluating the use of capecitabine in 26 patients in whom first- or second-line therapy with immunotherapy had failed found that 8.7% of patients exhibited a partial response.13 Another phase II trial evaluating the use of gemcitabine in 37 patients with metastatic or inoperable renal cell carcinoma yielded a response rate of 8.1%.

Multiple studies have been done evaluating combination chemotherapy regimens for advanced-stage renal cell carcinoma. Clinical trials evaluating the safety and efficacy of combinations using 5-fluoropyrimidines and gemcitabine are currently under way. Two recent trials using different combinations of capecitabine and gemcitabine have reported a partial response rate of 15%, with 53% of patients having stable disease.15,16 Another trial using a combination of gemcitabine and 5-fluorouracil has demonstrated a partial response rate of 17%. However, until more information is available, combination chemotherapy for metastatic renal cell carcinoma remains investigational.

The chemoresistance exhibited by renal cell carcinoma is unexplained, and consequently, unlike other solid tumor treatments, chemotherapy is not commonly pursued as treatment for advanced kidney cancer. The NCCN guidelines recommend single-agent chemotherapy as an option for first-line treatment of metastatic renal cell carcinoma in patients with non–clear cell histology.

Lilleby W, Fossa SD. Chemotherapy in metastatic renal cell cancer.World J Urol. 2005 Feb 22

Amato RJ. Chemotherapy for renal cell carcinoma. Semin Oncol. 2000;27:177-186., Kidney cancer

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