A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: preliminary results

OBJECTIVE: Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. This study was a preliminary result of a randomized two arms, prospective, open-label phase III trial comparing the activity and safety of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin alone in locally advanced cervical cancer. MATERIALS AND METHODS: The stage IIB-IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225 mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min, weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin alone concurrent with standard radiotherapy (Group B). RESULTS: Four hundred and sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The tumor response at 3-month follow-up time showed no significant difference. The only prognostic factor to improve the complete response rate was the hemoglobin level. The patients in Group A, who had Hb <10 gm/dL had the relatively better change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI 1.07, 2.04). No severe toxicity or adverse event had been reported. The median follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively. There was no statistical difference in PFS and OS. CONCLUSION: Concurrent chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor response rate or treatment toxicity compared to carboplatin alone. The combination drugs might have benefit in poor prognostic patients such as the baseline Hb <10 gm/dL.     

Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer

To evaluate the efficacy of incomplete treatment protocols of cisplatin in concurrent chemoradiation for locally advanced cervical carcinoma. This retrospective study was performed in 165 consecutively treated patients with locally advanced cervical cancer who received a weekly cisplatin regimen. The number of weekly cisplatin cycles of each patient was recorded and used to discriminate between patients. Local control, disease free survival, distant metastasis-free survival, and toxicities were calculated using the software package SPSS version 15.0. Ninety-two patients (55%) completed the planned protocol of six cycles of weekly cisplatin. With the median follow-up time of 38.2 months, the 3-year local control rate differed significantly in the two patient groups (95.4% of 6 cycles versus 84.8% of < 6 cycles; p = 0.028). No statistical significance was observed for disease-free survival (74.6% versus 74.5%; p = 0.22) and distant metastasis-free survival (76.5% vs. 75.7%; p = 0.88). In conclusion, the plan completion of concurrent cisplatin with radiotherapy was responsible for better local control. However, differences in disease-free survival and distant metastasis-free survival were not statistical significant.     

Randomized phase III trial of concurrent chemoradiotherapy vs accelerated hyperfractionation radiotherapy in locally advanced head and neck cancer

The aim of this study was to compare the efficacy and safety of concurrent chemoradiotherapy (CCRT) vs accelerated hyperfractionation with concomitant boost (CCB) as a primary treatment for patients with Stage III–IV squamous cell carcinoma of head and neck (SCCHN). A total of 85 non-metastatic advanced SCCHN patients were accrued from January 2003 to December 2007. Of these, 48 and 37 patients received CCRT and CCB, respectively. The patients were randomized to receive either three cycles of carboplatin and 5-fluorouracil plus conventional radiotherapy (CCRT, 66 Gy in 6.5 weeks) or hybrid accelerated radiotherapy (CCB, 70 Gy in 6 weeks). The primary endpoint was determined by locoregional control rate. The secondary endpoints were overall survival and toxicity. With a median follow-up of 43 months (range, 3–102), the 5-year locoregional control rate was 69.6% in the CCRT arm vs 55.0% in the CCB arm (P = 0.184). The 5-year overall survival rate was marginally significantly different (P = 0.05): 76.1% in the CCRT arm vs 63.5% in the CCB arm. Radiotherapy treatment interruptions of more than three days were 60.4% and 40.5% in the CCRT arm and CCB arm, respectively. The median total treatment time was 55.5 days in the CCRT arm and 49 days in the CCB arm. The rate of Grade 3–4 acute mucositis was significantly higher in the CCB arm (67.6% vs 41.7%, P = 0.01), but no high grade hematologic toxicities were found in the CCB arm (27.2% vs 0%). CCRT has shown a trend of improving outcome over CCB irradiation in locoregionally advanced head and neck cancer.     

Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial

PurposeThis single centre, open labelled, randomised non-inferiority trial compared concurrent chemoradiotherapy with carboplatin versus standard concurrent chemoradiotherapy with cisplatin in patients with locoregionally advanced nasopharyngeal cancer (NPC).Patients and methodsFrom August 1999 to December 2004, 206 patients with locally advanced NPC were randomised with 101 to cisplatin arm and 105 to carboplatin arm. Planned radiotherapy was the same in both groups. All the patients were evaluated for toxicity and survival according to the as-treated principle.ResultsWith a median follow-up of 26.3 months (range 3–74.6 months), 59% of patients in the cisplatin arm completed the planned concurrent chemoradiation treatment, compared to 73% in the carboplatin arm. Forty-two percent of cisplatin patients completed the 3 cycles of adjuvant therapy compared to 70% in the carboplatin group. There were more renal toxicity, leucopenia, and anaemia in the cisplatin group, and more thrombocytopenia in the carboplatin arm. The 3 year disease free survival rates were 63.4% for the cisplatin group and 60.9% for the carboplatin group (p = 0.9613) (HR 0.70, 95% confidence interval (CI): 0.50–0.98). The 3 year overall survival rates were 77.7% and 79.2% for cisplatin and carboplatin groups, respectively (p = 0.9884) (HR 0.83, 95% CI: 0.63–1.010).ConclusionWe concluded that the tolerability of carboplatin based regimen is better than that of the cisplatin regimen. Moreover, the treatment efficacy of carboplatin arm is not different from the standard regimen in the treatment of locoregional advanced stage NPC.     

Gemcitabine plus cisplatin (GC): a salvage regimen for advanced breast cancer patients who have failed anthracycline and/or taxane therapy

BACKGROUND: In clinical studies of both heavily and minimally pretreated patients with advanced breast cancer, the combination of Gemcitabine plus cisplatin (GC), given in a variety of schedules and doses, has demonstrated moderate safety and efficacy in both heavily and minimally pretreated advanced breast cancer with response rate from 29-63% (median 46%). METHODS: We evaluated the activity and toxicity of another GC regimen (gemcitabine 1,000 mg/m(2) days 1, 8 plus cisplatin 75 mg/m(2) day 1 every 3 weeks) in 30 breast cancer patients who failed chemotherapy with anthracycline and/or taxanes as adjuvant or neoadjuvant, or primary therapy. RESULTS: We obtained overall response in 15 of 29 evaluable patients (52%), with responses occurring in all subgroups of disease (unresectable locally advanced, locoregional recurrence, and distant metastasis). Toxicity was primarily hematologic, with grade 3/4 neutropenia and thrombocytopenia in 37% and 17% of patients, respectively. The only grade 3/4 non-hematologic toxicity was grade 3 nausea/vomiting in 12% of patients. CONCLUSION: Our data suggest that gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in anthracycline and/or taxane pretreated patients with advanced breast cancer.     

Oral cavity cancers at a young age: analysis of patient, tumor and treatment characteristics in Chiang Mai University Hospital

Oral cavity cancer is predominantly a disease of middle-aged men who use tobacco and alcohol. Nearly 95% of carcinomas occur after the age of 45, with an average age of approximately 60 years. In recent years, oral cavity cancers have increased at a younger age, especially in females who never consumed alcohol or smoked. The purpose of this study is to provide the information of these cancers in young patients treated in our hospital during a 5-year period. As well as to describe the treatment modalities and their results. We reviewed the medical records of oral cavity cancer patients occurring before the age of 45 who were treated at Chiang Mai University Hospital from 1999 to 2003. All the demographic data, histopathology, treatment modalities and their results were recorded. Follow up range from 0.7 to 4.4 years (mean 2.6 year). A total of 20 patients were studied. There were 12 male (60%) and 8 female (40%). The mean age was 34.4 year (20-40 year). The most common site was oral tongue (15 patients, 75%). Fifty-five percent of patients were stage III and IV. Only 6 patients (30%) were treated by surgery alone, 8 patients (40%) were treated by surgery and post-operative radiotherapy, 4 patients (20%) were subjected to radiotherapy alone, and 2 patients (10%) were treated by radiochemotherapy. The results of primary treatment in all modalities were acceptable with 5 patients (25%) developing loco-regional recurrence of disease within 10.8 months (2-36). At the time of analysis, 13 patients (65%) had no evidence of disease. The demographic data of oral cavity in younger patients in our hospital were different from the elderly, with oral tongue commonly occurring. Most of the patients were locally advanced stage. The results of all treatment modalities provided fair loco-regional control suggested more aggressive treatment in this group of patients.     

Preoperative irinotecan/5-FU/leucovorin plus concurrent radiotherapy in rectal cancer

PURPOSE: To evaluate results of preoperative irinotecan/5-FU/leucovorin plus radiotherapy for locally-advanced rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer were treated with preoperative irradiation 46 Gy plus concurrent chemotherapy(irinotecan 10 mg/m(2)/d d1-d5, d22-d26, 5-FU 350 mg/m(2)/d d1-d5, d22-d26, and leucovorin 20 mg/m(2) d1-d5, d22-d26), followed by radical surgery. RESULTS: There were no treatment-related deaths. Acute toxicity was mainly in neutropenia and diarrhea, with both grade 4 neutropenia and grade 3 diarrhea observed in 4 patients(11%). Radical resectability was performed in 29 patients(83%)with sphincter preservation surgery in 7 patients. Six patients did not undergo the planned surgery due to patient refusal and disease progression. A complete pathological response was observed in 14%(4/29). Pathological T-downstaging was observed in 55%(16/29). CONCLUSIONS: These results suggest that preoperative radiochemotherapy with irinotecan/5-FU/leucovorin is safe and effective in tumor downstaging and allows sphincter-saving resection to be performed in locally-advanced rectal cancer.     

Cancers in northern Thailand

A retrospective study was undertaken to assess cancers in northern Thailand using the Chiang Mai Cancer registry and Maharaj Nakorn Chiang Mai Hospital records from January 2001 to December 2005. Maharaj Nakorn Chiang Mai Hospital is the university hospital for the Faculty of Medicine, Chiang Mai University. There were 4,108 new cancer cases being treated at the institution. The distribution of patients were (a) 32% from Chiang Mai, (b) 42% from nearby provinces of Lampoon, Phayao, and Chiang Rai, (c) 20.4% from other northern provinces, and (d) 1.2% from other parts of Thailand. Based on the data, the most common cancers by relative frequency are cancers of the lung, cervix, liver, breast, and non-Hodgkin's lymphoma. The current treatment options used to manage these most common cancers are described in this article.     

Combination of vinorelbine + doxorubicin in advanced breast cancer

OBJECTIVE: To assess the efficacy of a vinorelbine + doxorubicin combination in terms of response rate and time to progression in patients with locally advanced or metastatic breast cancer. METHODS: Vinorelbine (25 mg/m2) and doxorubicin (25 mg/m2) were administered intravenously in a rapid injection on days 1 and 8 every 21 days. Initially, 3 courses of vinorelbine + doxorubicin were given. Patients with responding or stable disease received 6 more courses to a maximum of 9 courses. RESULT: Twenty-nine patients were entered into the study and 27 eligible patients were considered evaluable for response. Median age was 45 years (range 33 to 63). Overall response rate was 66.67% (18/27) (CR = 5, PR = 13). Median time to progression was 7.8 months (range 4 to 16) and the median survival time was 25.9 months. Median follow-up time was 8.5 months (range 1.5 to 25). Toxicity was generally moderate. Hematologic complication was the dose limiting toxicity. WHO grade III/IV neutropenia was observed in 18.5%/3.7% of patients. The major non-hematologic toxicities were nausea and phlebitis. Grade III nausea/vomiting was observed in 7.4% and grade III/IV phlebitis in 3.7%/3.7% of patients. No toxic deaths were observed. CONCLUSION: The present vinorelbine + doxorubicin combination was highly effective and generally well tolerated in cases of advanced breast cancer. Further studies are required.