Multicenter phase II clinical trial of preoperative capecitabine with concurrent radiotherapy in patients with locally advanced rectal cancer.

INTRODUCTION: To assess pathologic complete response, sphincter preservation rates and toxicity profile of preoperative chemoradiation with capecitabine in resectable locally advanced rectal cancer. MATERIALS AND METHODS: Fifty-eight patients from six Spanish centers were included (March 2004 to June 2005) with histological/cytological diagnosis of locally advanced rectal cancer, age between 18 and 80 years, ECOG 0-2, adequate bone marrow, renal and hepatic functions. Prior chemotherapy/radiotherapy was not allowed. Preoperative treatment was capecitabine 825 mg/m(2) bid concomitant to radiotherapy (45 + 5.4 Gy boost over 5.5 weeks). Surgery was performed 4-8 weeks after completion of chemoradiotherapy. RESULTS: Fifty-eight patients were enrolled in this study: 60.3 % males, median age of 64.5 (30.9-78.7) years, 28.6 % with ECOG 0 and 71.4 % with ECOG 1. Median distance of tumor from the anal verge was 7 (1-12) cm. Fifty-two (89.6. %) patients completed preoperative chemoradiotherapy. Primary tumor and node downstaging occurred in 61.1 and 69.6 % of patients, respectively. Surgery was performed in 55 patients (94.8 %): 80 % had negative lymph nodes and 72.7 % underwent sphincter-preserving procedures. A pathologic complete response was observed in 10.5 % (95 % CI 2.5-18.5) of the patients. Main grade I-II toxicities were leucopenia (43.1 %), neutropenia (24.1 %), anemia (36.2 %), diarrhea (32.8 %) and skin disorders (5.1 %), from which diarrhea (6.9 %), leucopenia (1.7 %) and skin disorders (1.7 %) reached grade III. There were no grade IV toxicities. CONCLUSIONS: Preoperative capecitabine-based chemoradiation is a well-tolerated and effective neoadjuvant treatment for locally advanced rectal cancer that achieves encouraging rates of tumor downstaging.

[Development of a questionnaire to evaluate the impact of hot flashes in quality of life in patients with advanced prostate cancer. The ESCAPA study]. / Desarrollo de un cuestionario sobre la repercusión de los sofocos en la calidad de vida de los pacientes con cáncer de próstata avanzado. Estudio ESCAPA.

BACKGROUND AND OBJECTIVE: Although the use of the androgen deprivation in advanced prostate cancer (APC) is extended, the impact of one of its frequent secondary effects, hot flashes, remains not deeply studied. Our aim is the design and validation of a specific questionnaire to evaluate the impact of hot flashes in APC patients with hormonal ablative treatment. PATIENTS AND METHOD: Observational, prospective, multicenter study of 496 patients with APC, who were included in one of 2 groups -A (reliability): 56 patients without expected significative state changes; and B (sensitivity): 440 patients, who were either naïve or under changes in hormonal therapy because of intolerance or disease progression-, during 9 months. Hot Flashes Questionnaire (19 items) and the Rotterdam Symptoms Checklist (RSCL) were administered. Variables as disease stage, prostate-specific antigen and Karnofsky index were collected. RESULTS: Response rate of questionnaire: 85.5%. Correlations observed between different items were high, ranging from 0.545 to 0.957. Effect size between initial visit and follow-up were 0.34, 0.41 and 0.53 at 3, 6 and 9 months. At 3 months, patients with progression showed a mean reduction (standard deviation) of hot flashes impact on daily life activities of 35.76 (37.05). Intern consistency, measured through Cronbach alpha, was of 0.98. Test-retest reliability, measured through intraclass correlation coefficient, resulted significative (0.84; 95% confidence interval, 0.69-0.91). CONCLUSIONS: Hot Flashes Questionnaire presents good results in feasibility, validity, reliability and sensitivity to change. It's the first questionnaire in evaluating hot flashes impact on APC patients, showing good measure properties that make proper its use both for clinical practice and investigation.

Induction chemotherapy with cisplatin/docetaxel versus cisplatin/5-fluorouracil for locally advanced squamous cell carcinoma of the head and neck: a randomised phase II study.

A combination of cisplatin and 5-fluorouracil (PF) is considered the standard induction chemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN). The present study compares the efficacy and safety of a new combination of cisplatin/docetaxel versus the PF regimen. A total of 83 chemotherapy-naive patients with locally advanced SCCHN were randomised to receive every 21 d (i) docetaxel 85 mg/m2 i.v. on day 1 and cisplatin 40 mg/m2 i.v. on days 1 and 2 (arm A) or (ii) cisplatin 100 mg/m2 i.v. on day 1 followed by 5-fluorouracil 1000 mg/m2 in 24 h continuous infusion for 5 d (arm B). A total of 287 cycles (range 1-3 per patient) were administered. Among 76 patients evaluable for response, the overall response rate in arm A was 70% (complete response (CR) 26%, partial response (PR) 44%) and in arm B 69% (CR 16%, PR 54%), respectively. Median survival in arm A was 7.6 months (95% CI: 5.8-11.1) and 9.9 months (95% CI: 7.4-14.6) for arm B. The most frequent grade 3/4 toxicity in arm A was neutropaenia (34.1%) and diarrhoea (9.8%) versus mucositis (29.3%) and neutropaenia (19.5%) in arm B. Both schedules present a similar efficacy, with different but acceptable toxicity patterns.

Cost-minimisation analysis of three regimens of chemotherapy (docetaxel-cisplatin, paclitaxel-cisplatin, paclitaxel-carboplatin) for advanced non-small-cell lung cancer.

PURPOSE: To compare the efficiency (the evaluation of efficacy in relation to costs) of three first-line treatment options for advanced non-small cell lung cancer (stage IIIB and IV) used in the Eastern Cooperative Oncology Group (ECOG) study: docetaxel/cisplatin (75/75 mg/m(2)/day, 1 h intravenous (i.v.) infusion of docetaxel), paclitaxel/cisplatin (175/75 mg/m(2)/day, 3 or 24 h i.v. infusion of paclitaxel) and paclitaxel/carboplatin (175/400 or 225/400 mg/m(2)/day, 3 h i.v. infusion of paclitaxel). METHODS: The results of the ECOG 1594 phase III clinical trial (Proc. Am. Soc. Clin. Oncol. 19 (2000) 2) demonstrated equivalent efficacy (survival, objective response) between the treatment options. To differentiate between the treatment options, we performed a cost-minimisation analysis, using a pharmacoeconomic model. RESULTS: The average estimated treatment cost per patient (median, 4 cycles) with docetaxel/cisplatin would be 1067836 Spanish pesetas (Ptas) (6418 Euros; 5741 US dollars (USD)), 1365304 or 1439369 Ptas (8205 or 8651 Euros; 7340 or 7738 USD) with paclitaxel/cisplatin (3 or 24 h infusions, respectively), and 1417995 or 1616784 Ptas (8522 or 9717 Euros; 7623 or 8692 USD) (paclitaxel dose of 175 or 225 mg/m(2)/day, respectively) with paclitaxel/carboplatin. CONCLUSION: According to our study, the treatment option docetaxel/cisplatin, with equal efficacy, would result in a cost saving of between 297468 and 548948 Ptas (1788 and 3299 Euros; 1599 and 2951 USD) per patient treated. This difference is mainly due to the lower treatment cost of docetaxel.