High frequency of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin.

INTRODUCTION: The combination of chemotherapy and thoracic radiation is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). However, most favorable chemotherapy regimen, timing of full-dose chemotherapy, and optimal combination of chemotherapy with radiation remain to be determined. Our primary objective was to evaluate the efficacy and safety of gemcitabine concurrent with radiotherapy after induction chemotherapy with gemcitabine plus carboplatin for locally advanced NSCLC. PATIENTS AND METHODS: Patients with histologically proven NSCLC stage IIIA and -B received carboplatin (area under the curve of 2.5) and gemcitabine (800 mg/m) on days 1 and 8, every 21 days for two cycles, followed by conventional fractioned thoracic radiotherapy and concomitant weekly gemcitabine 200 mg/m, and finally, consolidation chemotherapy. RESULTS: Inclusion was discontinued because of high-grade 3 to 5 radiation-pneumonitis events (6 of 19 patients, 31.6%), including one treatment-related death associated with radiation pneumonitis. Median follow-up was 11.9 months. Most common grades 3/4 hematological side effects comprised anemia, neutropenia 3 of 19 patients, each (15.8%), and thrombocytopenia (4 of 19, 21.1%) during induction. Partial response was observed in 10 patients (52.6%) following induction chemotherapy. After concurrent chemo-radiotherapy, overall response was 68.4%. Four patients (21.1%) underwent surgical resection. Median progression-free survival and overall survival were 12 +/- 1 month (95% confidence interval [CI], 9.8-14.1) and 21 +/- 3.5 months (95% CI, 14-27.9 months), respectively. CONCLUSION: Concurrent radiotherapy with gemcitabine after induction with gemcitabine and carboplatin showed a high-response rate; however, it is associated with excessive pulmonary toxicity. Adjustments in gemcitabine dosage during radiotherapy or changes in radiotherapy planning could reduce toxicity.

Human chorionic gonadotropin as an angiogenic factor in breast cancer during pregnancy.

Breast cancer associated with pregnancy is defined as the one in which the diagnosis is made in a pregnancy or within one year of delivery. Breast cancer is the second most common malignancy during pregnancy and it is generally considered to have a worse prognosis than the one that is not associated with pregnancy. The average patient is between 32 and 38 years of age. Steroid hormone receptor-positive cell populations comprise 80% of breast cancers, however, estrogen receptor levels in pregnancy-associated tumors are often low or absent. Extensive laboratory data suggest that angiogenesis plays an essential role in breast cancer development, invasion, and metastasis. One of the most powerful stimulatory factors, vascular endothelial growth factor (VEGF), functions in autocrine/paracrine pathways. Current research, generally has validated the poor prognosis and early relapse that are associated with increasing microvessel density, which is related to VEGF expression in tumoral cells. During pregnancy, human chorionic gonadotropin (hCG) induces neovascularization in various tissues, one of them being the placenta. Its receptors have been detected in epithelial cells in breast carcinoma tissue, and breast cancer cell lines. According to this premise the hCG normally produced during pregnancy could induce the synthesis of VEGF and by this means stimulate the development and metastatic potential of breast cancer cells in the pregnancy period. Thus, research involving hCG and VEGF would help us understand the physiopathology of breast cancer during pregnancy, as well as provide us with probable prognostic tools.