Capecitabine and Oxaliplatin Prior and Concurrent to Preoperative Pelvic Radiotherapy in Patients With Locally Advanced Rectal Cancer: Long-Term Outcome.

BACKGROUND: The risk/benefit ratio of any treatment can only be fully assessed if long-term results of both efficacy and toxicity are taken into account. Whereas the combined modality treatment of locally advanced rectal cancer (LARC) has considerably improved prognosis, particularly with regard to local control, long-term results-including patient-reported outcomes-are underreported. PATIENTS AND METHODS: Patients with LARC treated within a multicenter single-arm phase II study were prospectively assessed for at least 5 years after surgery. Study treatment consisted of capecitabine and oxaliplatin prior and concurrent to preoperative pelvic radiotherapy followed by total mesorectal excision. Progression-free survival time (first endpoint), overall survival time, and pattern of relapse were analyzed in the whole study population and in pre-planned exploratory subgroups. Patient-reported outcomes, including overall satisfaction with bowel, stoma, and urinary function, were assessed in 6-month intervals. RESULTS: Five-year progression-free and overall survival rate was 61% (95% confidence interval [CI], 46%-73%) and 78% (95% CI, 63%-87%), respectively. Distant to local recurrence rate was 3:1, with only 8% of patients relapsing locally. Main predictors for recurrence in univariate analyses were tumor downstaging (hazard ratio, 0.16; 95% CI, 0.05-0.56; P = .0011) and nodal downstaging (hazard ratio, 0.17; 95% CI, 0.06-0.52; P = .0005). The self-reported burden of symptoms related to bowel function was high in up to one-third of patients. A total of 28% of patients were dissatisfied with their urinary, bowel, or stoma function for at least 1 observation period. CONCLUSION: Combined-modality treatment of LARC results in a high and durable local disease control rate, especially in patients with tumor and/or nodal downstaging, at the cost of relevant long-term toxicity. Long-term care is required for a proportion of patients with poor gastrointestinal and/or urinary function after multimodality therapy. Reporting of long-term follow-up, including patient-recorded outcomes should be mandatory for future trials in LARC.

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.

A phase II, open-label study of gefitinib (IRESSA) in patients with locally advanced, metastatic, or relapsed renal-cell carcinoma.

Epidermal growth factor receptor (EGFR) expression has been associated with clinical outcome in some studies of renal-cell carcinoma (RCC). We investigated the efficacy and safety of gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, in RCC patients. This phase II trial recruited 28 patients with advanced, metastatic, or relapsed RCC. Patients received oral gefitinib 500 mg/day. Objective responses (ORs) were assessed every 2 months according to RECIST. Baseline tumor biopsies were analyzed immunohistochemically for EGFR expression. At trial closure (March 2003), no ORs were seen but 14 patients (53.8%) had stable disease. At extended analysis (August 2004), median time to progression was 110 days (95% confidence interval [CI]: 55, 117); median overall survival was 303 days (95% CI 180, 444). Gefitinib was generally well tolerated. Skin rash and diarrhea were the most common drug-related adverse events (AEs) [54 and 39% of patients, respectively] and the most common drug-related grade 3/4 AEs (both 11%). The majority of tumor biopsies (91%) had > or =70% of tumor cells expressing membrane EGFR. Despite the lack of ORs in this study, disease control was observed in 53.8% of patients. Gefitinib was generally well tolerated and no unexpected drug-related AEs were observed.

Circulating deoxyribonucleic Acid as prognostic marker in non-small-cell lung cancer patients undergoing chemotherapy.

PURPOSE: Circulating cell-free DNA is present in increased amounts in the blood of cancer patients, but the clinical relevance of this phenomenon remains unclear. We conducted a clinical study to assess the value of circulating DNA as a prognostic marker in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A standard protocol for the quantification of circulating DNA by real-time polymerase chain reaction was set up and validated at two oncology units. One hundred eighty-five informed patients with NSCLC and 46 healthy controls were included in the study. DNA concentrations were determined in paired plasma and serum samples and analyzed for a relationship with leukocyte counts and lactate dehydrogenase (LDH) levels. DNA concentrations in healthy controls and in patients were compared, and cutoff levels for plasma and serum DNA were determined. Patient survival was analyzed relative to baseline DNA concentrations, and the relationship between tumor responses and changes in DNA concentrations was assessed in patients receiving chemotherapy. RESULTS: We found a significant correlation between increased plasma DNA concentrations and elevated LDH levels (P = .009), advanced tumor stage (P < .003), and poor survival (P < .001). Tumor progression after chemotherapy was significantly (P = .006) associated with increasing plasma DNA concentrations. Serum DNA concentrations strongly correlated (P < .001) with leukocyte counts. CONCLUSION: Our data demonstrate that quantification of plasma DNA is an accurate technique amenable to standardization, which might complement current methods for the prediction of patient survival. This approach might be considered for evaluation in large prospective studies.

Peritoneal carcinoma in a male patient.

Peritoneal carcinoma is a rare primary tumor, described in the literature almost exclusively in women. This report describes our clinicopathological findings in a 51-year-old male patient with peritoneal carcinoma and ascites. Pathologic studies included routine histology, immunohistochemistry and electron microscopy on biopsy and autopsy tumor tissue. After chemotherapy, the patient achieved a complete remission twice, lasting for 14 months and 8 months, respectively, and died after 3 years. His clinical course was similar to that of female patients with peritoneal carcinoma or advanced ovarian cancer. Our case confirms the existence of primary peritoneal carcinoma in males. In addition, it shows that this entity responds to the same chemotherapy as used for ovarian cancer and primary peritoneal carcinoma in females.