Cinta Pallares

Phase III Study Comparing Cisplatin Plus Fluorouracil to Paclitaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Head and Neck Cancer

PURPOSE To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). PATIENTS AND METHODS Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). RESULTS A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). CONCLUSION Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.

Multicenter, Phase II Trial of Sunitinib in Previously Treated, Advanced Non–Small-Cell Lung Cancer

PURPOSE Aberrant vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) signaling have been shown to play a role in non-small-cell lung cancer (NSCLC) pathogenesis and are associated with decreased survival. We evaluated the clinical activity and tolerability of sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor that blocks the activity of receptors for VEGF and PDGF, as well as related tyrosine kinases in patients with previously treated, advanced NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC for whom platinum-based chemotherapy had failed received 50 mg/d of sunitinib for 4 weeks followed by 2 weeks of no treatment in 6-week treatment cycles. The primary end point was objective response rate (ORR); secondary end points included progression-free survival, overall survival, and safety. RESULTS Of the 63 patients treated with sunitinib, seven patients had confirmed partial responses, yielding an ORR of 11.1% (95% CI, 4.6% to 21.6%). An additional 18 patients (28.6%) experienced stable disease of at least 8 weeks in duration. Median progression-free survival was 12.0 weeks (95% CI, 10.0 to 16.1 weeks), and median overall survival was 23.4 weeks (95% CI, 17.0 to 28.3 weeks). Therapy was generally well tolerated. CONCLUSION Sunitinib has promising single-agent activity in patients with recurrent NSCLC, with an ORR similar to that of currently approved agents and an acceptable safety profile. Further evaluation in combination with other targeted agents and chemotherapy in patients with NSCLC is warranted.

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer

Background:Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC).Methods:We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety.Results:Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) ⩾8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated.Conclusions:The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC.

Pharmacogenetics of the DNA repair pathways in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.

Genetic variants in DNA repair genes may play a role in the effectiveness of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We analyzed 17 SNPs in eight genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XRCC1 and XRCC2) involved in DNA repair mechanisms and its association with outcome in NSCLC. This prospective study included patients with stages III and IV treated with platinum-based chemotherapy. All patients (n = 161) received cisplatin or carboplatin plus a third-generation drug. Additionally, stage IIIA and IIIB patients (n = 74) received concomitant or sequential radiotherapy. Germline polymorphisms were analyzed using the BioMark system in blood DNA samples. We found that in stage III patients, response was significantly associated with SNPs in ERCC1 and in ERCC3 genes, while radiotherapy-derived toxicity correlated with SNPs in the ERCC2 gene. In stage IV patients, response was associated with a genetic variant in the ERCC4 gene and survival with a SNP in the XRCC1 gene. The complexity of the DNA repair mechanisms along with the heterogeneity in the treatment of lung cancer could explain the role of multiple genes as putative biomarkers of patient outcome.

Ovarian carcinoma preceded by cerebral metastasis: review of the literature.

A patient with an asymptomatic primary ovarian carcinoma preceded several months before by a solitary intracranial metastasis is reported. The rarity of this phenomenon, the therapeutic experience in this patient, and the possible mechanism of spread are discussed. Also, a review of the literature is made.

Cisplatin and intravenous continuous infusion of bleomycin in advanced and metastatic esophageal cancer

Thirty-four patients with locally advanced or metastatic esophageal cancer were treated with cisplatin 35 mg/m2/day x 3 days in bolus, plus bleomycin 15 mg/day x 3 days, as an 18 h infusion, every 21-28 days. Twenty-nine are evaluable for response. Objective response was seen in 15 (52%, 95% confidence limits 35-69%) patients. Toxicity was mild. Twelve patients with locoregional disease were treated with this combination followed by radiotherapy and three of them are alive without disease at 18, 22 and 36 months. This combination warrants further study in the setting of combined treatment.

CHOP chemotherapy of intermediate and high-grade non-Hodgkin's lymphoma.

The results of CHOP treatment in 63 patients with intermediate and high-grade non-Hodgkins lymphoma (Working Formulation D to I), Ann Arbor stage I to IV were analyzed. The response rate was 87%, 71% complete remission and 16% partial remission with a mean duration of 22 months. The 5-year actuarial survival was 61% (95% confidence interval, 51-70%). The treatment was well tolerated and no deaths due to acute toxicity were observed. Poor prognostic factors in univariate analysis were: high-grade histology, stages III and IV, B symptoms, > or = 4 affected lymph node regions, Karnofsky index < or = 70, erythrocyte sedimentation rate (ESR) > 60 mm, haemoglobin < 100 g/l and elevated lactic dehydrogenase (LDH). Poor prognostic factors in multivariate analysis were: high-grade histology, stages III and IV, haemoglobin < 100 g/l and elevated LDH. In summary, good results were obtained with CHOP chemotherapy, without severe toxicity.

Mesotelioma maligno pleural. Características clínicas, factores pronósticos y tratamiento

El mesotelioma maligno pleural es una enfermedad letal a corto plazo con independencia del tipo de tratamiento realizado. Se han analizado de forma retrospectiva las caracteristicas clinicas, los factores pronosticos y los tratamientos realizados en 41 pacientes seguidos en los ultimos 13 anos en un servicio de oncologia. El 32% de los pacientes tenia una exposicion previa al asbesto, el 61% ≤ 60 anos, el 71% un indice de Karnofsky ≥ 80% y el 63% un estadio I de Butchart. El primer sintoma al diagnostico fue el dolor en el 66% de los casos y la mediana de tiempo desde el primer sintoma al primer diagnostico fue de 3 meses. Treinta pacientes nunca obtuvieron una remision completa (RC) de su enfermedad: 15 tratados con quimioterapia (QMT) paliativa, uno radioterapia (RT) paliativa, 5 con pleurectomia parcial (PP) mas RT y/o QMT y 9 con tratamiento sintomatico de soporte. Solo 11 (27%) pacientes obtuvieron una remision completa de su enfermedad al Analizar el tratamiento: 7 pacientes tratados con neumonectomia extrapleural, 2 ciclos de QMT y RT y 4 pacientes tratados con PP con o sin RT y/o QMT posterior. Solo tres de estos pacientes estan vivos sin recidiva a mas de un ano de seguimiento. La mediana de supervivencia de los 41 pacientes fue de 8 meses. En el analisis univariado, los factores pronosticos que influenciaron la supervivencia fueron la edad y el indice de Karnofsky. El grupo seleccionado de pacientes tratados inicialmente con cirugia obtuvo una supervivencia superior. En conclusion, solo el indice de Karnofsky y la edad fueron factores pronosticos en nuestra serie. La mejor supervivencia de los pacientes tratados inicialmente con cirugia estaria en relacion con la seleccion previa de estos.

A phase II trial of carboplatin in untreated patients with extensive stage small cell lung cancer

Twenty‐five untreated patients with extensive stage small cell lung cancer (ESSCLC) were treated with carboplatin (CBDCA) (500 mg/m2) given as a 24‐hour infusion every 21 days. Thirteen patients responded for an overall response rate of 52% (95% confidence limits, 32% to 72%) with 3 complete responses (CR) (12%; 95% confidence limits, 0% to 25%). The median duration of response was 4.5 months. The median survival time was 8 months with three long‐term survivors (12%) at 27, 33, and 43 months from the start of CBDCA treatment. Ninety‐two courses of CBDCA were administered and one treatment‐related death occurred. The main toxicity was myelosuppression. Grade 3 or 4 hematologic toxicity (hemoglobin level, < 8 g/dl; granulocyte count, < 1900/μl; and platelet count, < 49,000/μl) was observed as follows: neutropenia in 7 courses (8%) and in 7 patients (28%), decreased hemoglobin level in 13 courses (15%) and in 7 patients (28%), and decreased platelet count in 10 courses (11%) all Grade 3 and in 8 patients (32%). This study demonstrates that at this dose and schedule CBDCA is a highly active drug in ESSCLC and it has tolerable toxicity.

Anemia hemolítica microangiopática y metástasis cardiaca por carcinoma de cabeza y cuello

Microangiopathic haemolytic anemia (MAHA) complicates occasionally clinical evolution of disseminated tumors, usually adenocarcinoma-type, but is association with a squamous cell cancer of head and neck origin is rare. Additionally, head and neck cancer is an unusual origin of cardiac metastases. We present a patient with head and neck squamous cell cancer who developed intravascular haemolysis with thrombopenia. Postmortem study showed tumor cells into the heart and tumor emboli in pulmonary arterioles, the later often described in the cases of MAHA. We discuss the physiopathology of MAHA and its association with cancer. We briefly discuss epidemiology and pathogeny of cardiac metastases.