Tolerability Of Capecitabine Research Articles

An open-label, multicenter phase II trial of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors

The objective of this multicenter phase II trial was to evaluate the efficacy and tolerability of capecitabine in patients with cisplatin-refractory or relapsed germ cell tumors. Between March 2003-June 2004, 14 patients refractory to at least two regimens of cisplatin-based chemotherapy or with relapse after high-dose chemotherapy and autologous peripheral blood stem cell transplantation received 1250 mg/qm capecitabine orally twice daily for 14 days in 3-week cycles. Treatment was continued until tumor progression. All patients were heavily pretreated with a median number of four previous lines of chemotherapy (range, 2-11) and 86% had relapsed after high-dose chemotherapy with peripheral blood stem cell transplantation. No patient responded to study treatment. Nine patients (64%) had progressive disease after two cycles. Two patients already stopped treatment after one cycle, because of a clinically overt tumor progression. One patient died of his tumor progression at the end of the second cycle. Two patients received four cycles of capecitabine, as progression was less than 30%. The median survival time was 4 months (range, 0-10). The toxicity profile was favorable. Eighty-six percent of the cycles could be applied without dose modifications or delay. Grade III/IV toxicities (diarrhea and anorexia in one patient each) occurred in 7% of the cases. No hematotoxicity grade III/IV was observed. Neutropenia grade I/II was documented in 21%, anemia in 35% and thrombocytopenia in 14% of the patients. Capecitabine was well tolerated, but is not effective in heavily pretreated patients with cisplatin-refractory or relapsed germ cell tumors.

Detailed analysis of a randomized phase III trial: can the tolerability of capecitabine plus docetaxel be improved without compromising its survival advantage?

In a phase III trial, 3-weekly capecitabine (1250 mg/m(2) twice daily days 1-14) plus docetaxel (75 mg/m(2) day 1) demonstrated significantly superior overall survival to 3-weekly docetaxel (100 mg/m(2) day 1). We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy. Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered. More patients receiving capecitabine/docetaxel (65%) had dose reductions for adverse events than docetaxel alone (35%). In most patients requiring dose reduction with the combination (80%), capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2) and 55 mg/m(2), respectively. Subsequently, there were fewer cycles (17%) with grade 3/4 adverse events than with the full doses (34%). Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles. Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy. This retrospective analysis, as well as multiple phase II studies of taxanes with reduced-dose capecitabine, shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer. In addition, reducing the dose of both agents may be appropriate.

Multicenter phase II study of oral capecitabine plus irinotecan as first-line chemotherapy in advanced colorectal cancer: A Korean Cancer Study Group Trial

A phase II study was conducted to assess the efficacy and tolerability of capecitabine in combination with irinotecan (CAPIRI) in advanced colorectal cancer. Forty-seven patients with previously untreated metastatic or unresectable colorectal adenocarcinoma received capecitabine 1000 mg/m2 twice daily on days 2–15 and intravenous irinotecan 100 mg/m2 on days 1 and 8, every 21 days. A total of 268 cycles of chemotherapy (median 6: range 1–11) were administered. According to an intent-to-treat analysis, the overall response rate was 49% (95% CI, 35–63%). Median time to progression and overall survival were 7.5 months (95% CI, 4.8–10.2) and 19.5 months (95% CI, 15.7–23.8), respectively. The most common grade 3/4 adverse events were diarrhea (24%) and neutropenia (11%). There were no treatment-related deaths. These results indicate that CAPIRI has comparable activity and tolerability to FOLFIRI as first-line treatment for advanced colorectal cancer.

The evolution of fluoropyrimidine therapy: from intravenous to oral.

Chemotherapy for advanced colorectal cancer is based on i.v. 5-fluorouracil (5-FU). Numerous attempts have been made to increase the therapeutic benefit of 5-FU through schedule modification and biomodulation, but only modest improvements have been achieved. Capecitabine is an oral fluoropyrimidine that was developed in response to the clinical need for new therapeutic options offering improved efficacy, tolerability, and convenience for patients. Capecitabine was rationally designed to mimic continuous infusion 5-FU. It is rapidly and almost completely absorbed through the gastrointestinal wall and is converted to 5-FU via a three-step enzymatic cascade. 5-FU is generated preferentially in tumor by exploiting the higher activity of thymidine phosphorylase in tumor tissue compared with normal tissue. Results of a randomized, phase II trial led to the selection of a regimen of capecitabine for further clinical development (1,250 mg/m(2) twice daily for 14 days followed by a 7-day rest period). Subsequently, two large, randomized, phase III trials were conducted to compare capecitabine with i.v. bolus 5-FU/leucovorin ([LV]; Mayo Clinic regimen) in patients with metastatic colorectal cancer. A prospective, integrated analysis of data from the studies showed that capecitabine offers superior activity and an improved safety profile compared with 5-FU/LV. This article summarizes these developments in the treatment of colorectal cancer and assesses the feasibility of replacing i.v. 5-FU-based therapy with oral capecitabine. In addition, retrospective analyses assessing the impact of the dose modification scheme on the efficacy and tolerability of capecitabine are presented, and dose recommendations in special populations are reviewed.

The Role of Capecitabine, an Oral, Enzymatically Activated Fluoropyrimidine, in the Treatment of Metastatic Breast Cancer

Capecitabine is an oral fluoropyrimidine that mimics continuous infusion 5-fluorouracil and generates 5-fluorouracil preferentially at the tumor site. It is activated via a three-step enzymatic pathway, the final step of which requires thymidine phosphorylase, an enzyme that is significantly more active in tumor than normal tissue. As an oral agent, capecitabine is more convenient for patients and medical personnel, and avoids the complications associated with venous access. This paper reviews the development and clinical experience of capecitabine in breast cancer treatment. Clinical trials have established the efficacy and tolerability of capecitabine in anthracycline- and taxane-pretreated metastatic breast cancer, showing that capecitabine is an effective therapy for patients who have exhausted all established treatment options. Moreover, randomized, phase II studies have demonstrated that capecitabine is effective in anthracycline-pretreated patients and as first-line therapy for metastatic breast cancer. In addition to its confirmed efficacy, the favorable safety profile of capecitabine, particularly the low myelosuppression rate, makes it an attractive agent for incorporation into combination regimens. Therefore numerous trials have assessed the feasibility of capecitabine-containing regimens, and have shown promising results. Capecitabine is an important new treatment option for breast cancer patients, and ongoing clinical trials should further define its role in a range of settings.