Phase I study of concurrent and consolidation cisplatin and docetaxel chemotherapy with thoracic radiotherapy in non-small cell lung cancer.

BACKGROUND: We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc). METHODS: Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m2) and D given weekly. The starting dose of D was 20 mg/m2, escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated. RESULTS: Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m2. Consolidation D and C were each dose escalated to 75 mg/m2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43-110.8). CONCLUSIONS: The use of docetaxel 20 mg/m2 weekly and cisplatin 75 mg/m2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m2 every 3 weeks, appears to be safe in this phase i trial.

What are the factors that predict outcome at relapse after previous esophagectomy and adjuvant therapy in high-risk esophageal cancer?

OBJECTIVES: The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients. PATIENTS AND METHODS: From 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative crt therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative crt when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression. RESULTS: Of the 69 patients treated with adjuvant crt after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant crt had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003). CONCLUSIONS: Resection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant crt therapy.

Preoperative or postoperative therapy for stage II or III rectal cancer: an updated practice guideline.

AIMS: Uncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence? MATERIALS AND METHODS: The MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review. RESULTS: Systematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice. CONCLUSIONS: Preoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Acute nickel toxicity in electroplating workers who accidently ingested a solution of nickel sulfate and nickel chloride.

Thirty-two workers in an electroplating plant accidently drank water contaminated with nickel sulfate and chloride (1.63 g Ni/liter). Twenty workers promptly developed symptoms (e.g., nausea, vomiting, abdominal discomfort, diarrhea, giddiness, lassitude, headache, cough, shortness of breath) that typically lasted a few hours but persisted 1-2 days in 7 cases. The Ni doses in workers with symptoms were estimated to range from 0.5 to 2.5 g. In 15 exposed workers who were tested on day 1 postexposure, serum Ni concentrations ranged from 13 to 1,340 micrograms/liter and urine Ni concentrations ranged from 0.15 to 12 mg/g creatinine. Ten subjects (with initial urine Ni concentrations greater than 0.8 mg/g creatinine) were hospitalized and treated for 3 days with intravenous fluids to induce diuresis, resulting in a mean elimination half-time (T1/2) for serum Ni of 27 hours (SD +/- 7 hour), which was significantly shorter (p less than .001) than the mean T1/2 of 60 hours (SD +/- 11 hours) in 11 subjects who did not receive intravenous fluids. Laboratory tests showed transiently elevated levels of blood reticulocytes (N = 7), urine albumin (N = 3), and serum bilirubin (N = 2). All subjects recovered rapidly, without evident sequellae, and returned to work by the eighth day after exposure.