Capecitabine monotherapy and in combination with immunotherapy in the treatment of metastatic renal cell carcinoma

Abstract

This prospective trial aimed to evaluate the therapeutic effects and systemic toxicities of capecitabine monotherapy and capecitabine treatment combined with biological response modifiers in patients with metastatic renal cell carcinoma. Fifty-four patients suffering from metastatic renal cell carcinoma progressing under first-, second- or third-line treatment entered the trial. Capecitabine was given orally at a dose of 2500 mg/m2 daily divided into two doses for 14 days, followed by a 7-day rest in the monotherapy as well as in the combination treatment. This schedule was repeated in 3-week cycles. The combination therapy consisted of capecitabine and an immunotherapy treatment, which consisted either of interferon (IFN)-gamma1b (100 mg/day) administered consecutively 5 times weekly during weeks 1 and 2, and recombinant interleukin (IL)-2 (4.5 MU/day) administered on 4 consecutive days during weeks 3 and 4, every 6 weeks, or IFN-alpha (6 MioIE/day) administered 3 times a week. Fifty-two patients are now evaluable for response and 54 patients for toxicity. We observed a partial response to treatment in five patients (9.6%), minor response in five patients (9.6%), stable disease in 32 patients (61.6%) and only 10 patients (19.2%) showed continued disease progression despite treatment. Outpatient capecitabine was well tolerated. We did not observe any WHO grade IV toxicities. We conclude that capecitabine monotherapy and capecitabine treatment in combination with biological response modifiers appear to be effective regimens with favorable toxicity profiles in patients with advanced renal cell carcinoma. Capecitabine monotherapy seems to be superior than the combination treatment because of its easier application form.

Chemotherapy in metastatic renal cell carcinoma today? A systematic review

“…in the subgroup analysis (CB 91.7 vs. 66.7%), highlighting the importance of the timing of chemotherapy in treatment planning [19]. Considering the response rate (RR) of 15-20% reached by the standard first-line immunotherapy based on IL-2 or IFN-a [80,81], capecitabine treatment, combined or not with immunotherapy, led to a huge overall RR to in this study, 19.2%, (including both PR, defined as 50% or greater reduction of the tumor mass, and MR, defined as 25-50% decreased tumor size, according to the World Health Organization criteria) [82].…”

Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches

“…The authors reckon that this combination regimen has at least modest activity in patients with metastatic RCC. Wenzel et al (2003) used capecitabine, an orally administered fluoropyrimidine carbamate that is activated by a three-step enzymatic conversion to 5-FU, to treat several patient cohorts with metastatic RCC refractory to immunotherapy in second-and third-line settings. In a subgroup of 24 patients who received second-line capecitabine monotherapy at 2500 mg/m 2 daily divided into two doses for 14 days, followed by a 7-day rest, the authors observed a clinical benefit in 22 patients (92%).…”

A Phase II Study of Gemcitabine and Capecitabine in Patients With Advanced Renal Cell Cancer

“…Clinical trials of 5-fluorouracil (5FU) and its oral analog, capecitabine, have shown modest activity for these agents in RCC 14,15. Other studies have similarly shown modest activity of gemcitabine in RCC 16,17.…”