Nattokinase with the introduction of several new active agents including irinotecan, oxaliplatin, bevacizumab, and cetuximab/panitumumab. In addition, the oral pro drug of 5 FU, capecitabine, has been demonstrated to be at least equally eYcacious as 5 FU as a single agent and is also associated with less myelosuppression and mucositis. Furthermore, capecitabine is more convenient as an extended intravenous infusion is not required and has been suggested to be potentially more cost eVective. The combination of capecitabine and irinotecan has been extensively evaluated. There is no evidence of pharmacokinetic interactions between these twoagents and in initial studies the combination appeared to be well tolerated. Several phase II studies Chondroitin have been conducted to evaluate XELIRI as Wrst line therapy for mCRC. In these studies, response rates ranged from 35 to 49%, similar to response rates seen with infusional 5 FU or bolus 5 FU and irinotecan in phase III trials. The most frequently observed severe toxicities were diarrhea and neutropenia.
However, two subsequent randomized phase III trials raised concern about the potential toxicity of the capecitabine and irinotecan combinations with high rates of severe diarrhea and neutropenia, ZD6474 and several treatment related deaths. It is not clear if the toxicity noted was related to the dose of capecitabine and/or irinotecan in these studies, but it is possible that dose reductions in one or both agents may result in reduced toxicity and still maintain eYcacy for this combination. In 2004, Hurwitz and colleagues demonstrated that the addition of bevacizumab to standard chemotherapy as Wrstline therapy for mCRC resulted in a signiWcant survival advantage compared with chemotherapy alone. In this study, progressive free survival and research chemicals library overall survival were signiWcantly improved with the addition of bevacizumab to irinotecan and bolus 5 FU chemotherapy.
To evaluate the safety and eYcacy of dose reduced capecitabine and irinotecan given in combination with bevacizumab, we conducted a phase II study of this regime in patients with previously untreated metastatic or unresectable recurrent colorectal cancer. Patients and methods Patient selection Patients were eligible if they had metastatic or unresectable recurrent colorectal cancer and had not received prior chemotherapy for metastatic or recurrent disease. They were required to be 18 years of age, eastern cooperative oncology group performance status ?, adequate organ function, platelet count 100 109/L, normal serum creatinine and bilirubin, aspartate aminotransferase and alanine transaminase ?.0 the upper limit of normal, unless liver metastases were present. Patients were required to have measurable disease by response evaluation criteria in solid tumors 1.0. Exclusion criteria included concurrent other malignancies and any serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment. In addition, patients were excluded if they had metastasis of the central nervous system or a history of uncontrolled gastrointestinal bleeding, thromboembolism, hypertension, or proteinuria. The study was approved by the institutional ethics review board, and all patients provided written informed consent. Chemotherapy Capecit.