The secondary end points included toxicity, OS, overall response rate and quality of life. An analysis on survival, toxicity and Celastrol QoL analysis was done in a modified intent to treat population. The modified ITT population was defined as all randomly assigned patients who received chemotherapy at least once. The ORR was evaluated in the modified ITT population with measurable lesion. Survival curves were generated using the Kaplan Meier method and compared by the log rank test. AnColorectal cancer is the second most common neoplasm and the third leading cause of cancer related mortality in the United States according to data from the National Cancer Institute. Worldwide, over 1 million patients are diagnosed annually and 50% of these will develop metastatic disease.
1 Since the introduction of oxaliplatin and irinotecan, the combination of these drugs with 5 fluorouracil and leucovorin is considered standard chemotherapy for metastatic colorectal cancer.2 4 More recently, the addition of target therapy such as bevacizumab, cetuximab, and panitumumab have improved outcomes, but advanced disease remains mostly incurable.5 Rifapentine clinical trial 7 Third and fourth line treatments are often offered to patients whose disease progressed after exposure to the most active regimens and still have a good performance status. Since 1968, mitomycin C, an antitumour antibiotic, has been widely evaluated in the mCRC scenario.8 Due to in vitro data showing synergistic effects ofMMC and 5FU, this combination has been preferred by oncologists.
9 To better evaluate the role of MMC in the treatment of mCRC, we conducted a large retrospective study including 109 patients from three different institutions in two countries.The data presented in this retrospective analysis was obtained from the tumour registry Bleomycin structure of three institutions: Hospital Sı´rio BMS-354825 solubility Libaneˆs, M. D. Anderson Cancer Center, and Instituto do Caˆncer do Estado de Sa˜o Paulo, Faculdade de Medicina, Universidade de Sa˜o Paulo. HSL and MDACC are reference cancer centres that treat mainly private and insured patients. ICESP is a recently open public teaching hospital that provides evidence based care considering cost effectiveness for patients with no insurance and has more rigid protocols and limited access to the new monoclonal antibodies.
Patients were eligible if they had proven metastatic colorectal adenocarcinoma, defined by biopsy and imaging studies, and received at least one cycle of intravenous MMC based regimen. Patients who received intraperitoneal or intra arterial MMC or had predominantly neuroendocrine differentiation supply as the histology were excluded. All patients had progressed on previouschemotherapy regimens for metastatic disease based in 5FU, irinotecan and/or oxaliplatin. Progressive disease was confirmed by imaging studies in the majority of patients, but in some instances, patients who had clinical deterioration associated with increased tumour marker were considered to have PD.The administered dose of MMC varied between 6 to 10 mg/m2 every 4 6 weeks. Treatment was continued until PD or significant toxicity was observed. Dose reductions were made according to side effects. Tumour assessment was performed every two or three cycles and toxicity was evaluated at each cycle.