RESUMEN
BACKGROUND: Metastatic renal cell carcinoma (mRCC) treatment is still largely based on TKI use. Treatment adjustment due to toxicities is often needed. The aim of the present study was to determine the impact of treatment modifications on the outcome of mRCC patients treated with cabozantinib or pazopanib. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled consecutive patients receiving cabozantinib or pazopanib between January 2012 and December 2020. We evaluated the correlation of TKI treatment modifications with grade 3-4 toxicities and progression-free (PFS) and overall survival (OS). We also performed a landmark analysis excluding patients who did not undergo at least 5 months of therapy. RESULTS: Among 301 patients, 179 (59%) were treated with pazopanib, 122 (41%) with cabozantinib. Treatment modifications were related to grade 3-4 toxicities (p < 0.0001). We observed a statistically significant longer PFS and OS in patients who underwent dose reductions (p < 0.0001 for both PFS and OS), temporary interruption (p < 0.0001 for both PFS and OS) and schedule modifications (p = 0.007 for PFS and p = 0.012 for OS) at univariate analysis. These results were confirmed at multivariable and landmark analyses. CONCLUSIONS: Tailoring treatment with pazopanib and cabozantinib was associated with better PFS/OS.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Indazoles , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background Nonconformity to chemotherapy schedules is common in clinical practice. Multiple clinical studies have established the negative prognostic impact of dose delay on survival outcome. Objective This study investigated the prevalence and reason for chemotherapy schedule modifications of breast cancer patients. This study also investigated the impact of schedule modifications on overall survival (OS). Setting This retrospective cohort study was done among breast cancer patient receiving chemotherapy from 2013 to 2017 and patients were followed until 31 Dec 2018. Methods Medical records of patients with cancer were reviewed. Female patients over eighteen years old were included, with primary carcinoma of the breast, who received anthracycline or taxane based chemotherapy regime and completed more than two cycles of chemotherapy. Patients were categorized into three groups of (1) no schedule modification, (2) with schedule modification and (3) incomplete schedule. The Kaplan-Meier was used to test for survival differences in the univariate setting and Cox regression model was used in the multivariate setting. Main outcome measure Prevalence, overall survival rates and hazard ratio of three schedule group Results Among 171 patient who were included in the final analysis, 28 (16.4%) had no schedule modification, 118 (69.0%) with schedule modification and 25 (14.6%) had incomplete schedule with OS of 75.0%, 59.3% and 52.0% respectively. 94% (189) of all cycle rescheduling happened because of constitutional symptoms (70), for non-medical reasons (61) and blood/bone marrow toxicity (58). When compared to patients with no schedule modification, patients with schedule modification had a 2.34-times higher risk of death (HR 2.34, 95% CI 1.03-5.32; p = 0.043). Conclusion Nonconformity to the chemotherapy schedule is common in clinical practice because of treatment complications, patients' social schedule conflicts, and facility administrative reasons. Cumulative delays of ≥ 14 days are likely to have negative prognostic effect on patient survival. Thus, the duration of the delays between cycles should be reduced whenever possible to achieve the maximum chemotherapeutic benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Adulto , Neoplasias de la Mama/diagnóstico , Estudios de Cohortes , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule. METHODS: Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m2 on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m2 on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated. RESULTS: Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events. CONCLUSION: This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Center (ID: UMIN 000008491).