Comparison of Safety and Efficacy of Capecitabine in Conventional (2/1) v/s Continuous Dosing in Metastatic Breast Cancer and Colorectal Cancer Patients

Abstract

Cancer is unregulated multiplication of cells in the body. If such type of irregular proliferation is occurs in the lobules and milk ducts of breast is referred as breast cancer. In metastatic breast cancer tumor do not encapsulated, it shows invasion and metastasis to other organs. According to American cancer society 2017, In USA 30% cases of breast cancer were estimated amongst all other cancers. In India pproximately 21.5% of breast cancer cases were estimated according to world health organization. It is second most common cause of death in females. In colorectal cancer, abnormal growth of cells occurred in colon and rectum region, combined referred is as large intestine. It is considered as most common type of cancer in both male and female. According to American cancer society in 2017, in USA 9% of males and 8% of females having colorectal cancer were found. According to world health organization, 7.8% of males and 6.4% of females from colorectal cancer in India. Capecitabine is a pro-drug of 5-FU, which is administered orally after taking meal. Capecitabine is widely used in the treatment of MBC and MCRC patients. In conventional dosing regimen(continuously for 2 weeks (14 days) followed by 1 week (7 days) rest period) 2.5 to 3 gm/m2 per day was administered depending on patient’s weight. In continuous dosing regimen (without 7 days rest period) 1 gm/m2 per day was administered depending on patient’s weight. Objectives To determine whether continuous dosing is equally effective or less toxic as compared to conventional dosing capecitabine. To compare trough level of capecitabine in conventional v/s continuous dosing and correlate with efficacy and toxicity. Methodology The proposed study was single centric, prospective and observational study. All adults with metastatic breast cancer and metastatic colorectal cancer, who were treated with Capecitabine alone at Hemato-oncology clinic, Vedanta Institute of Medical Science, Ahmedabad were enrolled in the study. Counseling of patients was done for enrollment followed by signing theinformed consent form. Patients were provided with unique id to safeguard their identity. Patients were informed not to take regular dose of capecitabine (for both conventional and continuous dosing) in next planned visit, as he/she has to take medicine after collection of blood sample. Blood samples were collected and analyzed. At the visit between 6th and 9th week, CT scan and other laboratory tests was performed to assess the response. At every clinic visit, adverse events was assessed and recorded as per NCI CTC version 4.03. Results During the present study, we enrolled 20 patients from which 13 patients were suffering from metastatic breast cancer and 7 were suffering from metastatic colorectal cancer. Among these 20 patients, 12 patients were receiving conventional dosing of capecitabine and 8 patients were receiving continuous dosing of capecitabine. We found that haematological toxicities (anemia, leucopenia and thrombocytopenia) were less in continuous dosing arm as compared to conventional dosing arm. All variables such as serum creatinine, random blood sugar (RBS), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) were found within the range. There was no significant change was found with respect to before treatment in the (day 0) and after treatment group (day 10) of both the dosing regimen. The obtained data of non-haematological details of MBC and MCRC patients was suggestive that given treatment has not affected functions of liver, kidney and other organs of the body. Main toxicities of capecitabine are hand-foot syndrome, diarrhea and stomatitis. Along with this, nausea and vomiting were also seen as additional toxicities. From the obtained results, it was concluded that less toxicities were observed in continuous dosing arm as compared to conventional dosing arm. There was no significant difference in complete response, Partial Response, Stable Disease as well as Clinical Benefit Response (CR, PR, SD as well as CBR response respectively) of the treatment in patients of both the arms. Trough levels of capecitabine and 5-FU were found less in continuous dosing regimen as compared to the conventional dosing regimen.Conclusion Our study suggested that the efficacy of two arms was equivalent in terms of CR, PR, SD as well as CBR. Fewer patients who were on continuous dosing regimen required further dose reduction as compared to conventional dosing regimen patients. The frequency of haematological toxicity was observed to be less in patients on continuous dosing regimen as compared to conventional dosing regimen patients. Trough level of capecitabine and 5-FU was found less in continuous dosing regimen as compared to conventional dosing regimen, which indicated that continuous dosing of capecitabine produced less toxicity as compared to conventional dosing regimen.