Role of Chemotherapy With Gemcitabine Plus 5-fluorouracil and Chemoimmunotherapy in Metastatic Renal Cell Cancer (mRCC)

Abstract

Several phase II trials have shown that gemcitabine and fluoropyrimidines have marginal but definite activity in patients with metastatic renal cell cancer (mRCC). We retrospectively analyzed the 193 mRCC patients consecutively seen in our institutions during the last 11 years, of whom 39 were treated with chemotherapy (CT): 16 were treated with CT alone (gemcitabine and 5-fluorouracil) and 23 with the same regimen plus low dose of interleukin-2 and interferon-alpha. The main end point of the analysis was to estimate response rate and time to progression (TTP); the secondary end point was to evaluate overall survival (OS) and toxicity. Overall TTP was 3.2 months (95% confidence interval: 2.22-4.18). Three patients (7.7%) achieved a partial response and 10 (25.6%) stable disease. Median OS was 9.23 months (95% confidence interval: 7.16-11.31) and the 1-year survival rate was 40.6%. Although not statistically significant, the response and disease control rates were better in the pretreated patients (8% vs. 7% and 44% vs. 14%), with a favorable trend for TTP and OS (4.9 vs. 3.2 mo and 12.9 vs. 4.2 mo). Grade 3 to 4 toxicities included hematologic toxicity and depressed mood. OS was strongly influenced by performance status, the presence of brain metastasis, and response after 3 cycles of therapy. In these mRCC patients, both CT and chemoimmunotherapy showed modest but definite activity and a regimen CT-based should be offered to patients with progressive mRCC. The association of these treatments with antiangiogenetic agents should be tested in future trials.

Dose-finding Trial of a Combined Regsimen With Bevacizumab, Immunotherapy, and Chemotherapy in Patients With Metastatic Renal Cell Cancer: An Italian Oncology Group for Clinical Research (GOIRC) Study

“…5,6 The few published trials showed at the best an RR of <10% to 15%, with the combination of gemcitabine and 5-fluorouracil representing the best regimen. [15][16][17] In an earlier analysis of a series of mRCC patients treated with the combination of CT (gemcitabine+5-fluorouracil)+IT (low doses of IL-2+IFN-a), we described a modest but definite activity of this combination with a good disease-control rate and tolerability. 15…”

“…5,6 The few published trials showed at the best an RR of <10% to 15%, with the combination of gemcitabine and 5-fluorouracil representing the best regimen. [15][16][17] In an earlier analysis of a series of mRCC patients treated with the combination of CT (gemcitabine+5-fluorouracil)+IT (low doses of IL-2+IFN-a), we described a modest but definite activity of this combination with a good disease-control rate and tolerability. 15 The rationale for combining CT with anti-vascular endothelial growth factor (VEGF) drugs is based not only on preclinical data showing that anti-VEGF therapy normalizes tumor vascularization and improves the distribution of CT agents to tumoral cells, 18 but also on the results of clinical trials in other tumors 19 ; bevacizumab was the first antiangiogenic agent studied in a randomized double-blind phase II trial for the treatment of mRCC.…”

Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg)

“…A good activity of chemotherapy has been described by our group in patients with mRCC progressing to a regimen of low doses of IL-2+IFN-α [3]. Several studies also showed activity of chemotherapy alone or in combination with target therapy.…”

“…CT was rarely used against mRCC, and it was employed only for progressing, unresponsive patients [1,2]. The few published trial showed at the best a response rate (RR) of 10-15 %, with the combination of gemcitabine and 5-fluorouracil representing the best regimen [3,4]. In a previous analysis of a series of mRCC patients treated with the combination of chemotherapy (gemcitabine+5-fluorouracil) plus IT (low doses IL-2+IFN-α), we described a modest but definite activity of this combination with a good disease control rate and tolerability [3].…”

Rare Bone Metastases of the Olecranon

“…A recent study showed gemcitabine with 5-fluorouracil was able to stabilize disease in approximately 25.6% of metastatic renal cell patients. 12 Overall our patient's palliative chemotherapy and immunotherapy regimen did delay his initial skeletal event and subsequently postponed the development of his olecranon metastasis.…”