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BACKGROUND: Previous studies in sarcoma found that a composite gene signature, including high expression of nucleotide excision repair (NER) genes (XPG and/or ERCC1) and low expression of homologous recombination repair (HR) genes (BRCA1), identifies a highly sensitive population of patients with significantly improved outcome to trabectedin. This exploratory phase II trial evaluated a customized trabectedin treatment according to this gene signature in patients with non-small cell lung cancer (NSCLC) after the failure of standard platinum-based treatment. METHODS: Patients were selected according to their mRNA expression (elevated XPG and/or ERCC1, with low BRCA1) using the following values as cutoff: XPG=0.99, ERCC1=3.47 and BRCA1=12.00. Trabectedin was administered as a 1.3mg/m(2) 3-hour intravenous infusion every 3 weeks (q3wk). The primary efficacy endpoint was the progression-free survival rate at 3 months. Objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) was a secondary efficacy endpoint. RESULTS: Two of 18 evaluable patients (11.1%; 95% CI, 1.38-34.7%) achieved progression-free survival rate at 3 months. The primary efficacy objective (at least 3 of 18 patients being progression-free at 3 months) was not met, and therefore the trial was early finalized. No objective responses per RECIST were achieved. Four patients had stable disease. Median PFS was 1.3 months, and median overall survival was 5.9 months. Trabectedin was usually well tolerated, with a safety profile similar to that described in patients with other tumor types. CONCLUSIONS: Customized treatment with trabectedin 1.3mg/m(2) 3-h q3wk according to composite gene signature (XPG and/or ERCC1 overexpression, and BRCA1 underexpression) was well tolerated, but had modest activity in NSCLC patients pretreated with platinum. Therefore, further clinical trials with trabectedin as single agent in this indication are not warranted.

Introducción: Las opciones de tratamiento sistémico para los pacientes con cáncer de próstata hormonorrefractario (CPHR) que progresan a pesar del uso de docetaxel son muy limitadas. Una de las opciones de uso compasivo disponibles en la actualidad es el empleo de sunitinib. Presentamos una experiencia preliminar conjunta con el uso de sunitinib en esta circunstancia clínica. Pacientes y métodos: Se presenta una serie de 8 casos que refleja una experiencia multicéntrica prospectiva con sunitinib en pacientes con cáncer de próstata metastático, hormonorrefractario y en progresión, previamente tratados con al menos un régimen quimioterápico a base de docetaxel. En algunos pacientes ya se habían ensayado otros regímenes quimioterápicos alternativos. El objetivo primario de nuestro estudio fue la tasa de respuesta de PSA, y el objetivo secundario el tiempo libre de progresión. Se administró una dosis de 50mg/ día durante ciclos de 4 semanas, seguidos de 2 semanas de descanso por ciclo, hasta alcanzar un total de 8 ciclos o hasta la progresión clínica o toxicidad intolerable. Resultados: En 4 casos el PSA descendió por debajo del 50% del nivel basal al inicio del tratamiento, y 5 pacientes presentaron algún descenso del PSA. El tiempo libre de progresión fue de 16,4 semanas. La toxicidad derivada del tratamiento fue moderada y manejable. Conclusiones: A pesar de lo limitado de esta experiencia, podemos decir que sunitinib parece una opción activa y segura en pacientes con cáncer de próstata hormonorrefractario y resistente a quimioterapia con docetaxel. Introduction: Systemic treatment options for patients with hormone-refractory prostate cancer (HRPC) that progress despite the use of Docetaxel are very limited. One of the options of compassionate use currently available is the use of Sunitinib. We present a joint preliminary experience with the use of Sunitinib in this clinical case. Patients and methods: A series of eight cases is presented, which sets forth a prospective multicentre experience with Sunitinib in patients with hormone-refractory metastatic and progressive prostate cancer, previously treated with at least a regime of Docetaxel-based chemotherapy. Other alternative chemotherapy regimes had already been tried in some patients. The primary objective of our study was the PSA response rate and our secondary objective was the progression-free period. We administered a dosage of 50mg/day for four-week cycles, followed by a two-week rest per cycle, until we reached a total of eight cycles or up to clinical progression or intolerable toxicity. Results: In four cases, the PSA dropped to below 50% of the baseline level at the beginning of the treatment, and five patients presented some decrease in PSA. The progression-free time was 16.4 weeks. Toxicity arising from the treatment was moderate and manageable. Conclusions: Despite the limits of this experience, we can say that Sunitinib appears to be an active and safe option in patients with hormone-refractory prostate cancer that is resistant to chemotherapy with Docetaxel.

Platinum-based combinations are efficacious in the treatment of advanced non-small cell lung cancer (NSCLC) but their toxicity makes them unsuitable for elderly and for patients with co-morbidities. We assessed the efficacy and toxicity of low-dose of paclitaxel in patients who were elderly or who had contraindications against cisplatin therapy. Seventy-one patients (median age 68; range 42-82 years) with unresectable NSCLC were treated with weekly paclitaxel (80 mg/m2) infusion (1 h) for several cycles without intervening rest periods. Thirty-seven patients had PS 1 and 34 had PS 2 status. A total of 614 courses were administered (median 9, range 2-20). There were no episodes of grade 4 toxicities and only 1 patient had grade 3 thrombopenia. Grade 3 anemia or neutropenia were not observed and severe non-hematological toxicity was uncommon: grade 1-2 fatigue in 52%; grade 1-2 motor neuropathy in 42% and grade 3 in 5.5%; grade 1-2 sensory neuropathy in 46.3% of patients. Twenty-seven of the 67 evaluable patients (40.3%) had an objective response, whereas 26 patients (38.8%) had stable disease. The median overall survival for the entire group was 8.4 months (95% CI = 5.6 to 11.2) and the 1-year and 2-year survival was 37.4% and 12.1%, respectively. The median time-to-progression was 5.4 months (95% CI = 3.3 to 7.4). Our data show that low-dose weekly paclitaxel is active and well tolerated in this group of patients with NSCLC and poor prognosis and, as such, is useful for patients in whom platinum-based combinations are not suitable.

The results are reported of three chemotherapy schedules in a multicentric, international, randomized trial of the therapy of unresectable non small cell lung carcinoma which included 612 patients. The antitumoral efficiency of the cisplatin + vindesine combination (200 patients) was compared with that of navelbine (206 patients), a recently available vinca alkaloid, and with a third therapeutical leg with cisplatin + navelbine (206 patients). After a very thorough response evaluation the combination cisplatin + navelbine obtained a response rate higher than the other combination (30% vs. 19%; p = 0.02) and also than navelbine (30% vs. 14%; p0.001). The median response durations were 9.3, 9.9, and 7.8 months for the combination with navelbine, vindesine and the new vinca alkaloid alone, respectively. After a median follow-up period of 26 months the combination cisplatin + navelbine achieved a higher survival rate than the combination cisplatin + vindesine (40 vs. 32 weeks) and navelbine (40 vs 31 weeks; p = 0.045). The most important toxicity with the combination cisplatin + navelbine was neutropenia, which although relevant in number was not of long duration. In summary, navelbine is an active agent in the therapy of non small cell lung carcinoma. In this trial the therapeutic superiority of its combination with cisplatin over the combination cisplatin + vindesine was observed; likewise, it was also more efficient than monotherapy with navelbine.