Purpose: Although diabetes mellitus (DM) is recognized as a risk factor for chemotherapy-induced neurotoxicity, its true impact on intensity and time course of peripheral neuropathy is still unclear. The goal was to analyze the relevance of preexisting DM to weekly paclitaxel-induced peripheral neuropathy (PIPN). Methods: We performed a retrospective case-control study (1:2) including a total of 129 patients with breast cancer (43 with DM and 86 controls) treated with single-agent weekly paclitaxel (wP). Results: Compared with controls, patients with DM treated with wP experienced PIPN more frequently (74.4% vs 58.4%; P=.016) and with higher severity (grade 2–3: 51.2% vs 27.7%; P=.014). A significant delay in PIPN resolution was observed in women with DM (P=.001) and, in a multivariate analysis, DM was the only independent predictor for delayed recovery (hazard ratio [HR], 0.16; 95% CI, 0.05–0.55; P=.003). After 2 years, 68.7% of patients with DM (vs 29.2% of women without DM) still experienced PIPN, which was functionally significant (grade 2–3) in 18.2%. Conclusions: Significantly more dose delays and reductions because of PIPN occurred in patients with DM. Preexisting DM associates with long-lasting significant PIPN in patients treated with wP. Benefits and risks of long-term significant PIPN should be carefully balanced in patients with DM before starting wP chemotherapy.
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- Author: Elena García-Martínez x
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Pilar de la Morena Barrio, María Ángeles Vicente Conesa, Enrique González-Billalabeitia, Edgar Urrego, Elisa García-Garre, Elena García-Martínez, Marta Zafra Poves, Vicente Vicente, and Francisco Ayala de la Peña
Alberto Carmona-Bayonas, Paula Jiménez-Fonseca, Maria Luisa Sánchez Lorenzo, Avinash Ramchandani, Elena Asensio Martínez, Ana Custodio, Marcelo Garrido, Isabel Echavarría, Juana María Cano, Jose Enrique Lorenzo Barreto, Teresa García García, Felipe Álvarez Manceñido, Alejandra Lacalle, Marta Ferrer Cardona, Monserrat Mangas, Laura Visa, Elvira Buxó, Aitor Azkarate, Asunción Díaz-Serrano, Ana Fernández Montes, and Fernando Rivera
Background: There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients and Method: Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). Results: A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72–0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60–12.68) versus 9.60 months (95% CI, 8.44–10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65–0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64–0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60–1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63–0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. Conclusions: With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity.