Neoadjuvant radiotherapy combined with fluorouracil-cisplatin plus cetuximab in operable, locally advanced esophageal carcinoma: Results of a phase I-II trial (FFCD-0505/PRODIGE-3).

Background: Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20-25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab. Methods: A 45-Gy radiotherapy regimen was delivered over 5 weeks. The phase I study determined the dose-limiting toxicity and the maximum tolerated dose of 5FU-cisplatin plus cetuximab. The phase II trial aimed to exhibit a pCR rate > 20 % (25 % expected), requiring 33 patients (6 from phase I part plus 27 in phase II part). pCR was defined as ypT0Nx. Results: The phase I study established the following recommended doses: weekly cetuximab (400 mg/m2 one week before, and 250 mg/m2 during radiotherapy); 5FU (500 mg/m2/day, d1-d4) plus cisplatin (40 mg/m2, d1) during week 1 and 5. In the phase II part, 32 patients received C-RT before surgery, 31 patients underwent surgery, and resection was achieved in 27 patients. A pCR was achieved in five patients (18.5 %) out of 27. After a median follow-up of 19 months, the median progression-free survival was 13.7 months, and the median overall survival was not reached. Conclusions: Adding cetuximab to preoperative C-RT was toxic and did not achieve a pCR > 20 % as required. The recommended doses, determined during the phase I part, could explain these disappointing results due to a reduction in chemotherapy dose-intensity. Trial registration: This trial was registered with EudraCT number 2006-004770-27.

Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy.

INTRODUCTION: Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS: This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by six cycles of maintenance temozolomide (150-200 mg/m(2), five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS: One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5-15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3-4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS: This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3-4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients.

Evaluation of a 36 Gy elective node irradiation dose in anal cancer.

PURPOSE: To retrospectively analyze the efficacy of 36 Gy of elective node irradiation and report patterns of recurrence in patients with anal cancer treated by chemoradiation with the same radiotherapy (RT) treatment scheme. METHODS AND MATERIALS: Between January 1996 and December 2013, 142 patients with anal squamous cell cancer were scheduled to receive a dose of 36 Gy of elective node irradiation (ENI) to the inguinal area and whole pelvis over 4 weeks followed after a 2-week gap by a boost dose of 23.4 Gy over 17 days to the macroscopic disease. Mitomycin C combined with fluorouracil, capecitabin or cisplatin was given at day 1 of each sequence of RT. RESULTS: Disease stages were I: 3, II: 78, IIIA: 23, IIIB: 38. Compliance rates were 97.2% with RT and 87.9% with chemotherapy. After a median follow up of 48 months [3.6-192], estimated 5-year overall survival and colostomy-free survival were 75.4% and 85.3% respectively. Eleven patients (7.7%) never achieved a complete response, 15 had a local component of recurrence and 5 a regional one. One patient had failure in the common iliac node area outside the treatment fields. The inguinal control rate was 98.5%. The 5-year tumor and nodal control rates were 81.5% and 96.0%, respectively. CONCLUSION: Chemoradiation with a dose of 36 Gy ENI achieved excellent nodal control. However, it is necessary to improve the 5-year control rate of the primary tumor. Omitting the gap and using additional doses per fraction or hyper-fractionation are to be explored.

Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: preliminary results of a multicentre phase II trial.

BACKGROUND AND PURPOSE: We evaluate the feasibility of concomitant and adjuvant docetaxel combined with three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation in high-risk prostate carcinomas. METHODS: Fifty men with high-risk localized prostate cancer (16), locally advanced (28) or very high-risk prostate cancer (6) were included. Seventy Gy were delivered on prostate and seminal vesicles in 35 fractions, concurrently with weekly docetaxel (20mg/m(2)). Three weeks after the completion of 3D-CRT, docetaxel was given for 3 cycles (60mg/m(2)), every 3 weeks. Patients had to receive LHRH agonist during 3 years. RESULTS: The intent to treat analysis shows that four patients out of 15 stopped prematurely the chemotherapy due to grade 3-4 acute toxicity. In the per protocol analysis, 46 patients completed a full-dose chemoradiation regimen representing 413 cycles: five patients experienced a grade 3 toxicity, and 15 patients experienced a grade 2 toxicity. With a median follow-up of 54 months, the 5-year clinical disease-free survival was 66.72% and the 5-year survival was 92.15%. CONCLUSIONS: 3D-CRT with androgen deprivation and concurrent weekly docetaxel, followed by three cycles of adjuvant docetaxel may be considered as feasible in high-risk prostate cancer and deserved to be evaluated in a phase III randomized trial.

Feasibility of chemoradiotherapy for oesophageal cancer in elderly patients aged >or=75 years: a prospective, single-arm phase II study.

BACKGROUND: The number of elderly patients with oesophageal cancer is expected to increase with the aging of the population and the rapidly increasing incidence of adenocarcinoma. Surgical resection is standard treatment for patients with localized disease considered fit for operation. However, elderly patients with oesophageal cancer are rarely referred for surgery. The aim of this prospective, single-arm, phase II study was to evaluate the feasibility and efficacy (tumour response) of chemoradiotherapy in the treatment of elderly patients with localized oesophageal cancer. Secondary endpoints were progression-free survival (PFS) and quality of life (QOL). METHODS: The main study inclusion criteria were: patients aged >or=75 years; oesophageal cancer disease stage II-III; Charlson co-morbidity index score

Combining cisplatin and mitomycin with radiotherapy in anal carcinoma.

PURPOSE: The European Organization for Research and Treatment of Cancer (EORTC) phase II study No. 22953 demonstrated the feasibility of reducing the overall treatment time of chemoradiation, delivering mitomycin C twice rather than once and fluorouracil during the whole treatment. We tested the feasibility of chemoradiation in anal carcinoma with mitomycin and cisplatin in a phase II study. METHODS: Twenty-one patients with locally advanced anal carcinoma (15 women, 6 men) were treated. The first sequence of radiotherapy consisted of 36 Gy over four weeks. After a gap interval of 16 days, a second sequence of radiotherapy was given, delivering 23.4 Gy over 2.5 weeks. Mitomycin C was delivered at 10 mg/m(2) day 1 of each sequence and cisplatin was delivered at 25 mg/m(2)/week of each sequence. RESULTS: The compliance rates for the first sequence with radiation, mitomycinm, and cispaltin (dose and timing) were 100 percent. The median duration gap was 16 days (14-30 days). The compliance rates for the second sequence with radiation, mitomycin, and cisplatin (dose and timing) were 100, 76.2, and 85.7 percent, respectively. Grade > or = 2 acute toxicities of 62, 29, 25, and 5 percent were observed for skin, diarrhea, hematologic, and renal toxicities, respectively. Nineteen patients were in complete response (90.5 percent). CONCLUSIONS: Combining radiation with mitomycin and cisplatin in patients with locally advanced anal cancer is feasible. The results are promising. The EORTC is currently comparing this combination with mitomycin and 5-fluorouracil in a large phase II-III trial.

Tumor volume as outcome determinant in patients treated with chemoradiation for locally advanced esophageal cancer.

OBJECTIVE: The currently used tumor-node metastasis (TNM) staging method is generally not applicable to patients with unresectable esophageal carcinomas. There is a need for both an efficient, easy-to-perform clinical classification and for identification of pretherapeutic prognostic factors that would be useful for oncologists, one of which is tumor volume. METHODS: Records of 148 patients, admitted to hospital during the period January 1993 to December 2001, were evaluated retrospectively. Median age was 65.7 years (range, 35.5-85.5 years). Most patients had SCC (84.5%). Using the computed tomography (CT) scan classification, tumors were recorded as follows: 1 T1, 42 T2, 93 T3, 6 T4, 2 Nx, 72 N0, 74 N1. Tumor volume from the CT scans was determined as the sum of 2 opposed truncated cones. Median tumor volume was 57.5 cm3 (range, 0.6-288 cm3). RESULTS: Median follow-up was 15.1 month (range, 0.3-82.8 months). Survival rates at 1, 2, and 3 years were 42.5%, 21.6%, and 8%, respectively. Prognostic factors identified by univariate analysis were: dysphagia grade > or =2, other histology than squamous cell, tumor location below the carina, age <65 years and tumor volume > or =100 cm3. Prognostic factors identified with multivariate analysis were: dysphagia grade > or =2 (P = 0.013), weight loss > or =10% (P = 0.047), tumor location below the carina (P = 0.002), and tumor volume > or =100 cm3 (P = 0.041). CONCLUSIONS: For patients that the TNM staging system is not applicable, tumor volume is a new powerful determinant of survival. Further clinical trials need to be carried out to validate this prospectively.