ABSTRACT
INTRODUCTION: This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer. METHODS: Patients were randomized (2:1 ratio) to receive pemetrexed 500 mg/m(2) intravenously once every 3 weeks plus either oral pazopanib 800 mg daily or cisplatin 75 mg/m(2) intravenously once every 3 weeks up to six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. The primary endpoint was progression-free survival (PFS). RESULTS: The study was terminated after 106 of 150 patients were randomized due to a higher incidence of adverse events leading to withdrawal from the study and severe and fatal adverse events in the pazopanib/pemetrexed arm than in the cisplatin/pemetrexed arm. At the time enrolment was discontinued, there were three fatal adverse events in the pazopanib/pemetrexed arm, including ileus, tumor embolism, and bronchopneumonia/sepsis. Treatment with pazopanib/pemetrexed was discontinued resulting in more PFS data censored for patients in the pazopanib/pemetrexed arm than those in the cisplatin/pemetrexed arm. There was no statistically significant difference between the pazopanib/pemetrexed and cisplatin/pemetrexed arms for PFS (median PFS, 25.0 versus 22.9 weeks, respectively; hazard ratio = 0.75; 95% confidence interval, 0.43%-1.28%; p = 0.26) or objective response rate (23% versus 34%, respectively; 95% confidence interval, -30.6% to 7.2%; p = 0.21). CONCLUSION: The combination of pazopanib/pemetrexed in first-line treatment of non-small-cell lung cancer showed some antitumor activity but had unacceptable levels of toxicity.
Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/drug therapy , Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Large Cell/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma, Bronchiolo-Alveolar/mortality , Adenocarcinoma, Bronchiolo-Alveolar/pathology , Adult , Aged , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Female , Follow-Up Studies , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Indazoles , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pemetrexed , Prognosis , Pyrimidines/administration & dosage , Sulfonamides/administration & dosage , Survival RateABSTRACT
Soft tissue sarcomas are uncommon tumors of mesenchimal cell origin. Criteria for suspicion is a soft tissue mass that is increasing in size, and has a size greater than 5 cm or is located under the deep fascia. Diagnosis and management of these patients should preferably be performed by a specialist multidisciplinary team in a referral center. Assessment of a patient with a suspect of sarcoma should include magnetic resonance and biopsy performed prior to surgery. Primary local therapy for patients with localized sarcoma is based on wide surgical resection with a tumor-free tissue margin, in association in most cases with radiotherapy. Adjuvant chemotherapy constitutes an option that could be considered in high-risk sarcomas of the extremities. When metastasis are present, surgery of pulmonary lesions, in some selected patients, and chemotherapy are current available options.
Subject(s)
Practice Guidelines as Topic , Sarcoma/therapy , Adult , Algorithms , Decision Trees , Humans , Medical Oncology/legislation & jurisprudence , Neoplasm Metastasis , Neoplasm Staging/methods , Sarcoma/diagnosis , Sarcoma/pathology , SpainABSTRACT
La quimioterapia neoadyuvante (QTN) es el tratamiento de elección en las pacientes con cáncer de mama localmente avanzado e inflamatorio. Los objetivos de este tratamiento son mejorar las opciones quirúrgicas (convertir tumores inoperables en operables, así como obtener mejores resultados estéticos), determinar la respuesta a la quimioterapia (respuesta patológica completa [pCR, en sus siglas en inglés]) y aumentar la supervivencia libre de enfermedad. La QTN es una situación clínica ideal para investigar predictores moleculares de respuesta, predecir los pacientes que conseguirán una pCR y los pacientes con un pronóstico favorable, aunque no alcancen una pCR. Los estudios actuales definirán mejor el esquema óptimo de quimioterapia (nuevos fármacos) y los pacientes que más se beneficiarán de este tratamiento(AU)
Neoadjuvant systemic therapy (NST) has become widely accepted as the treatment of choice for patients with locally advanced and inflammatory breast cancer. In general, NST is used to improve the surgical options (induction of tumour shrinkage that may render inoperable tumours amenable to surgery and may allow smaller resection and better cosmetic outcome for patients with operable tumours), to determine the response to NST (pCR: pathologic complete response), and to obtain long-term disease-free survival. NST is an ideal clinical setting to discover molecular predictors of response to therapy, to predict patients who will achieve a pCR, and patients who will have a favourable prognosis despite not achieving a pCR. Current trials will better define the optimal NST (new drugs) and those patients who might best benefit from this therapy(AU)
Subject(s)
Humans , Female , Pregnancy , Adult , Neoadjuvant Therapy/methods , Neoadjuvant Therapy , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Pregnancy Complications, Neoplastic/drug therapy , Pregnancy Complications, Neoplastic/physiopathology , Neoadjuvant Therapy/trends , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/pathologyABSTRACT
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