ABSTRACT
Introduction: We conducted a multi-centric phase II study to evaluate the tumor response and safety of the combination of vinorelbin and docetaxel in treatment of metastatic breast cancer patients
Patients and methods: Forty one metastatic breast cancer patients, who had at least one measurable lesion and had not been treated for metastasis before, were enrolled from March 2006 to June 2009. Treatment contained vinorelbine 25mg/m2 IV and docetaxel 30mg/m2 at day 1 and 8. Cycles were repeated every 21 days for 6 cycles. We evaluated response to chemotherapy every three weeks and toxicity every week
Results: The mean age of patients was 50.4 years [range 30-81]. Twenty eight patients [68.2%] had received prior neoadjuvant anthracycline based chemotherapy. No patient had received adjuvant chemotherapy within the last 3 months. Twenty four patients [58.3%] had two or more metastatic sites. Thirty six patients were evaluable for their response. An objective tumor response [either complete response or partial response] was achieved in 32 [88.8%] and complete response was seen in 9 [25%] patients. Thirteen patients [31.6%] developed grade 3-4 neutropenia and neutropenic fever was reported in 11 [26.8%]. Grade 3 anemia was observed in 1 patient [2.4%]. No grade 4 non-hematological toxicity was noted and the most frequent grade 3 non-hematological toxicities were hair loss [39%], stomatitis [7.3%] and diarrhea [4.8%]. Median time to progression was 7 months and median overall survival was 11 months
Conclusion: Vinorelbine-docetaxel combination shows a considerable tumor response and manageable toxicity as the first line treatment for metastatic breast cancer. It seems logical to conduct phase III trials to further evaluate this regimen
ABSTRACT
Oxaliplatin [OX] significantly enhanced the antitumor activity of 5-FU in patients with advanced colorectal cancer and recently some phase II trials have evaluated the feasibility and efficacy of oxaliplatin in neoadjuvant setting for treatment of locally advanced rectal cancer. On the other hand various studies have demonstrated that the overexpression of thymidylate synthase [TS] can induce resistance to 5-FU in colorectal carcinoma. The aim of this study was to assess the value of TS expression as a predictive factor in the efficacy of neoadjuvant chemoradiation with and without oxaliplatin in rectal cancer. This study was performed in 61 patients [that ultimately 50 patients had including criteria] with locally advanced rectal adenocarcinoma that inferior margin of the tumor had to be located no farther than 6 cm from the anal verge. Preoperative radiotherapy was delivered to the pelvis with CO 60 to 50/4 Gy. All patients received simultaneous chemotherapy: 5-fluorouracil [5-FU], 300 mg/square meter i.v. 24 h infusion during radiotherapy on days 1-5 every week. Thirty patients received oxaliplatin 50-60 mg /square meter weekly during radiotherapy.TS expression was assessed by immunohistochemical staining technique in pretreatment specimen, and the patients were categorized into TS [+] and TS [-] groups. A total of 23 of 50 tumors showed TS positive status at biopsy [46%] . Overall 36 patients [72%] achieved pathologic response [40% complete and 32% partial] that was significantly better in the TS [-] group than in the TS [+] group [85.1 vs 56.5%, p=0.024] and in the OX [+] group than in the OX [-] group [86.6 vs 50%, p=0.005]. Among TS [-] patients there was no difference in pathologic response [88.2 vs 80%, p=0.561] or sphincter preservation [76.4 vs 80%, p= 0.831] as a result of whether oxaliplatin therapy was carried out or not. But among the TS [+] patients there was a significant gain in pathologic response [84.6 vs 20 %, p=0.002] and sphincter preservation [84.6 vs 40 %, p= 0.026] in favor of oxaliplatin group. Our study indicate that oxaliplatin can improves poor outcome of TS positive rectal cancer and TS expression may be used for selecting patients for oxaliplatin containing neoadjuvant chemoradiation protocols that can have major role in the tumor down staging and preservation of sphincter and ultimately better quality of life