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BACKGROUND: Patients with recurrent and metastatic head and neck Squamous Cell Cancer (HNSCC) have poor prognosis with limited treatment options. In view of decimal prognosis, the treatment decision should include quality of life (QOL) issues, cost-effectiveness besides the response rates and survival. AIM: Present retrospective analysis was conducted to evaluate efficacy (disease-free survival), pharmacoeconomics, and toxicity profile of four (4) different regimens, viz. gefitinib alone, gefitinib with methotrexate, methotrexate alone, or 5-FU with cisplatin. MATERIALS AND METHODS: Case records between 2007 September and 2008 September were analyzed, 68 patients were found suitable for analysis. Patients received gefitinib (250 mg/day), methotrexate as 50 mg intramuscular weekly or a combination of the same or 5-FU 750 mg/m(2)/day for 4 days along with cisplatin 75 mg/m(2)/day on day 1 in 21-day cycle. RESULTS: A total of 68 patients received therapy. Fifty-one patients have clinically meaningful response (stable disease + complete + partial responses) (75%) and had symptomatic improvement. The median progression-free survival was significantly superior in responders (those who achieved partial or complete response) (8.4 months vs. 3.1 months, P=0.001). Methotrexate with gefitinib had maximum median survival and better overall QOL compared to the other treatment regimens. Weekly methotrexate is relatively cost-effective followed by methotrexate with gefitinib and gefitinib alone. 5-FU with cisplatin in our experience does not appear so attractive in view of high complication rates (when given in full doses) and prolonged hospital stay. CONCLUSION: Based on the results of this retrospective analysis, methotrexate weekly as single agent or in combination with gefitinib appears as an attractive alternative regimen for patients with metastatic HNSCC including those having poor performance status. A prospective study was planned and submitted to the local ethics committee based on above results to validate these results and compare methotrexate and gefitinib arm with 5-FU + cisplatin.
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BACKGROUND: This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. METHODS: Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2:1 to also receive intravenous trebananib 10 mg kg(-1) once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). RESULTS: One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade ≥3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). CONCLUSION: Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Terapia Recuperativa , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Biomarcadores de Tumor/análisis , Camptotecina/administración & dosificación , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Método Doble Ciego , Femenino , Fluorouracilo/administración & dosificación , Humanos , Agencias Internacionales , Leucovorina/administración & dosificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Recombinantes de Fusión/administración & dosificación , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: One of the most distressing complications of head and neck cancer patients on chemoradiotherapy is mucositis. There is no proper tool to predict its occurrence in these patients. AIM: This study was conducted to develop a risk-scoring system to predict probable incidence and severity of mucositis in head and neck cancer patients on chemoradiotherapy. MATERIALS AND METHODS: This is a retrospective analysis conducted at a tertiary care cancer center with approximately 2,000 new cases of head and neck cancer patients annually. We Hypothesized were age, comorbid conditions, leukocyte count, nutritional status, oral hygiene, tobacco use, erythrocyte sedimentation rate (ESR); Eastern cooperative oncology group (ECOG) performance status (PS) and TNM (tumor, node, metastasis) stage as possible risk factors. Receiver operating characteristic (ROC) curves were drawn to predict the cutoff values for risk factors, and a final scoring system was developed with sensitivity and specificity data. RESULTS: A total of 218 patients on chemoradiation receiving cisplatin 40 mg/m2 /week along with local radiation of 60-70 Gy depending on primary site were analyzed. Based on ROC analysis, the following cutoff values were selected: age > 40 years, ECOG PS > 2, WBC < 3000/µL, elevated ESR, albumin < 3 gm/dL and > stage III disease. The remaining factors were indicated as present or absent. A score of 1 was assigned for the above risk factors. For patients, the final score of 3 or less there is 17% probability of developing grade 3 or 4 mucositis, while patients having score of 6 or more have 76% probability. CONCLUSION: The current tool is fairly accurate in predicting development of mucositis in head and neck cancer patients on chemoradiotherapy. This will further help clinicians to adopt preventive strategies as well as better counseling.
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Antineoplásicos/efectos adversos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Mucositis/etiología , Terapia Combinada , Neoplasias de Cabeza y Cuello/complicaciones , Humanos , Curva ROC , Radioterapia/efectos adversos , Estudios Retrospectivos , Medición de RiesgoRESUMEN
PURPOSE: Mucositis is a common and troublesome adverse effect of concurrent chemoradiotherapy, often causing treatment interruption and compromising treatment outcome. We sought to identify predictors of mucositis in southern Indian patients treated for gastroesophageal carcinoma. METHODS: Patients (N = 90) receiving cisplatin 40 mg/m(2) and concurrent local radiotherapy at 40 to 50 Gy for esophageal carcinoma were retrospectively assessed for predictors of mucositis. Hypothesized risk factors were age, presence of comorbid conditions, low white blood cell (WBC) count, nutritional status (assessed by serum albumin level), continuing tobacco use, elevated erythrocyte sedimentation rate (ESR) as a measure of acute inflammation, World Health Organization (WHO) performance status, and disease stage. Receiver operating characteristic (ROC) curves were drawn to identify cut-off values for risk factors, and a risk scoring model was developed. RESULTS: On the basis of cutoff values on ROC analysis, a risk score of 1 was assigned for each risk factor as follows: age > 50 years, ESR > 3 times upper limit of normal, albumin < 3.3 g/dL, WBC < 2.5 x10(9)/L, WHO performance status > 2, and > stage III disease, with use of tobacco and presence of any comorbid condition also each being assigned a score of 1. For individual patients, a score of < 3 was associated with a 25% risk of grade 3 or 4 mucositis, whereas a score of >/= 6 was associated with 80% risk. CONCLUSION: The scoring system is accurate in predicting the development of mucositis in southern Indian patients receiving concurrent chemoradiotherapy for esophageal carcinoma.
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In Bihar, India, where visceral leishmaniasis is hyperendemic, amphotericin B deoxycholate is now first-line parenteral treatment. To test the efficacy of amphotericin B deoxycholate versus that of its lipid formulations, Indian patients were randomized to receive treatment with amphotericin B deoxycholate (1 mg/kg on alternate days for 30 days; n=51), liposomal amphotericin B (2 mg/kg per day for 5 days; n=51), or amphotericin B lipid complex (2 mg/kg per day for 5 days; n=51). Infusion-associated reactions were frequent and persistent in subjects treated with amphotericin B deoxycholate. The illness of 3 patients failed to respond to treatment, and 5 patients experienced relapse. Final cure rates were similar. Estimated total treatment costs for a 25-kg patient-417 dollars for amphotericin B deoxycholate, 872 dollars for liposomal amphotericin B, and 947 dollars for amphotericin B lipid complex-differed as a result of drug cost. Substantial reductions (approximately 60%) in the price of liposomal amphotericin B and amphotericin B lipid complex would make treatment costs comparable to that of amphotericin B deoxycholate, permitting administration of short-course regimens in India.