Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

We investigated the clinical effects of low-power laser therapy (LPLT) on prevention and reduction of severity of conditioning-induced oral mucositis (OM) for hematopoietic stem cell transplantation (HSCT). We randomized 38 patients who underwent autologous (AT) or allogeneic (AL) HSCT. A diode InGaAlP was used, emitting light at 660 nm, 50 mW, and 4 J/cm2, measured at the fiberoptic end with 0.196 cm2 of section area. The evaluation of OM was done using the Oral Mucositis Assessment Scale (OMAS) and the World Health Organization (WHO) scale. In the LPLT group, 94.7% of patients had an OM grade (WHO) lower than or equal to grade 2, including 63.2% with grade 0 and 1, whereas in the controls group, 31.5% of patients had an OM grade lower than or equal to grade 2 (P < .001). Remarkably, the hazard ratio (HR) for grades 2, 3, and 4 OM was 0.41 (range, 0.22-0.75; P = .002) and for grades 3 and 4 it was 0.07 (range, 0.11-0.53; P < .001). Using OMAS by the calculation of ulcerous area, 5.3% of the laser group presented with ulcers of 9.1 cm2 to 18 cm2, whereas 73.6% of the control group presented with ulcers from 9.1 cm2 to 18 cm2 (P = .003). Our results indicate that the use of upfront LPLT in patients who have undergone HSCT is a powerful instrument in reducing the incidence of OM and is now standard in our center.

No abstract

No abstract

BACKGROUND: Cisplatin-based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin-based CRT (E 1 CRT) recommended a phase 2 erlotinib dose of 150 mg/day. METHODS: Eligibility criteria included International Federation of Gynecology and Obstetrics stage IIB to IIIB epidermoid cervical cancer, no prior therapy, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received erlotinib at a dose of 150 mg/day 1 week before and in combination with cisplatin (40 mg/m 2 administered weekly for 5 cycles) and radiotherapy (4500 centigrays in 25 fractions), followed by brachytherapy (4 fractions at a dose of 600 centigrays weekly). RESULTS: A total of 36 patients completed treatment with E 1 CRT. The median duration of therapy was 77 days and the median follow-up period was 59.3 months. The therapy was well tolerated overall, and 34 patients (94.4%) achieved a complete response. The 2-year and 3-year cumulative overall and progression-free survival rates were 91.7% and 80.6% and 80% and 73.8%, respectively. CONCLUSIONS: Treatment with E 1 CRT appears to be safe and exerts significant activity against locally advanced cervical cancer. To the best of the authors' knowledge, this is the first study to date to demonstrate that a target agent has promising activity against locally advanced cervical cancer. Cancer 2014;120:1187-93.

Purpose: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer. Experimental Design: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m 2 , weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB. Results: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL100 mg, and 8 at DL 150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity. Conclusions: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated.The maximum tolerated dose has been defined as150 mg.To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.

TP53 mutations are common in esophageal squamous cell carcinomas (SCC). To identify biological markers of possible relevance in esophageal SCC, we (i) searched for genes expressed in a p53-dependent manner in TE-1, an esophageal SCC cell line expressing the temperature-sensitive TP53 mutant V272M, and (ii) investigated the expression of one of those genes, the interferon-inducible Guanylate Binding Protein 2 (GBP-2), in esophageal SCC tissues. Clontech Human Cancer 1.2 arrays containing 1,176 human cancer gene-related sequences were used to identify differentially expressed genes in TE-1 cells at permissive (32°C) and nonpermissive (37°C) temperatures. The expression of GBP-2 and IRF-1, its main transcriptional regulator, was analyzed by immunohistochemistry in a retrospective series of 41 esophageal SCC cases with a clear transition zone from noncancer, apparently normal epithelium to invasive cancer. The expression of the GBP-2 gene is consistently increased in TE-1 at 32°C in a p53-dependent manner, as confirmed by inhibition of p53 expression by RNA interference. Increase in GBP-2 is accompanied by an increase in protein levels of IRF-1, the main transcriptional regulator of GBP-2, and in the formation of complexes between p53 and IRF-1. GBP-2 expression is significantly higher in esophageal SCC than in adjacent normal epithelium (p < 0.01), in which GBP-2 staining is limited to the basal layer. Our results suggest that p53 up-regulates GBP-2 by cooperating with IRF-1. The association of GBP-2 expression with proliferative squamous cells suggests that GBP-2 may represent a marker of interest in esophageal SCC.

Cervical cancer is a public health problem in Brazil, with annual incidence rates of 20-40 cases/100,000 women. Most patients with recurrent disease have symptoms from locoregional disease and may develop renal failure. This study aims to evaluate the outcome of patients with recurrent cervical cancer who underwent percutaneous nephrostomy (PN). We reviewed the medical records of 50 such patients who were referred to the Palliative Care Unit of the Brazilian National Cancer Institute from January 2002 to October 2006. Median age was 44 years (range, 26-67 years). Half the patients had improvement in pain or uremic symptoms, and seven (14%) had improved performance status (PS) after the procedure. Thirty patients (60%) had improvement of renal function; median creatinine levels before and after PN were 6.4 and 3.7mg/dL, respectively (P<0.05). Median overall survival after PN was 8.9 weeks (95% confidence interval [CI]: 7.4-10.3). Median survival was 9.9 weeks (95% CI: 8.7-11.0) in 40 patients with baseline PS 1-3 and one week (95% CI: 0.1-1.9) in 10 patients with PS 4 (log rank, P<0.0001). Median survival in patients with and without improvement of renal function after PN was 10.0 weeks (95% CI: 8.6-11.3) and 2.6 weeks (95% CI: 0-11.3), respectively (log rank, P=0.01). Twenty-nine patients (58%) died from renal failure. Complications were mainly urinary tract infection (n=10), catheter loss (n=9), and bleeding (n=1). These data suggest that PN can be of clinical benefit for carefully selected patients with recurrent cervical cancer.