14 febrero 2020
Tener 10 o más parejas sexuales eleva el riesgo de cáncer .
Tener un historial de 10 o más parejas sexuales está relacionado con un mayor riesgo de ser diagnosticado de un cáncer. Lo revela una investigación publicada en «BMJ Sexual & Reproductive Health» que asegura que, además, en el caso de las mujeres, el número de parejas sexuales también se asocia con otras enfermedades crónicas a lo largo de su vida. ...
SMALL CELL LUNG CANCER . New Drugs such as Lurbinectedin and Immunotherapy Are New Treatment Options.
Clinical Guides in Oncology
First Online: 10 February 2020 .
Authors :
M. Dómine // T. Moran // D. Isla // J. L. Martí // I. Sullivan // M. Provencio // M. E. Olmedo // // S. Ponce // A. Blasco // M. Cobo .
Abstract :
Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15–20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum–etoposide. In stage IIB–IIIC, the recommended treatment is early concurrent chemotherapy with platinum–etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum–etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment.
New Biomarkers and New clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.
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Second and successive lines in ES-SCLC
Despite SCLC being very responsive to initial therapy, most of the patients relapse with a mOS of 5–7 months. It is very important for the distinction of > 3 months (chemo-sensitive disease) or within 3 months (chemo-resistant or refractory disease). All patients with relapsed SCLC should be assessed for clinical trials. Decision treatment should include PS, comorbidities, toxicity, and disease-free interval from prior therapy. When a patient relapses more than 3 months after the first-line therapy, reinduction of the original regimen with platinum etoposide is recommended (II, B) [31]. If relapse occurs, 3 months or less must be considered administering single-agent therapy with IV or oral topotecan (I, B). An alternative is the combination CAV: cyclophosphamide–doxorubicin–vincristine (II, B). Other agents commonly used based on phase 2 trials are irinotecan, taxanes, gemcitabine, vinorelbine, or temozolomide [32]. Only around 20% of SCLC patients will receive the third-line therapy with modest results.
Several targeted therapies have been assessed without still satisfactory results. Rovalpituzumab is an antibody–drug conjugate directed against DLL3 (Notch signalling) with positive results in an initial trial [34], but negative in a phase 3 study against topotecan (TAHOE trial). Other studies with DLL3 inhibitors are ongoing. New drugs targeting other new pathways are in development, including DNA damage and repair (e.g. PARP inhibitors), epigenetics, and cell cycle.
Immunotherapy with immune checkpoint inhibitors has demonstrated modest activity in relapsed SCLC patients (nivolumab +/− ipilimumab, pembrolizumab, atezolizumab, and durvalumab + tremelimumab) without clear predictive biomarker identification; and the only phase 3 study carried out comparing nivolumab vs standard chemotherapy (CheckMate 331) was negative [35]. New immunotherapy drugs and combinations remain promising. Patients whose progress while on immunotherapy as part of first-line therapy should not be treated with other immune checkpoint inhibitors (see Fig. 2).
Definitely, predictive biomarker-driven therapies are needed with the aim to improve the current still poor outcomes in relapsed SCLC. New classification of SCLC subtypes defined by distinct gene expression profiles could help us to design new clinical trials [36]. Schedules regimens for second and successive lines are described in Table 2.
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