Does Rapid Drug Desensitization to Chemotherapy Affect Survival Outcomes?

BACKGROUND AND OBJECTIVE: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. Objective: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. METHODS: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). RESULTS: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). CONCLUSIONS: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients.

Does rapid drug desensitization to chemotherapy affect survival outcomes?

BACKGROUND: Hypersensitivity reactions to oxaliplatin may affect prognosis by jeopardizing the timely completion of scheduled treatment sessions or by forcing reactive patients into unexpected changes in therapy. Rapid drug desensitization (RDD) enables these patients to receive their first-choice treatments safely. However, the possible effects of RDD on the efficacy of oxaliplatin have never been studied. OBJECTIVE: The objective of this study was to evaluate the effect of RDD on survival rates in oxaliplatin-hypersensitive patients. METHODS: We performed a 7-year retrospective study to compare survival between oxaliplatin-hypersensitive cases (patients receiving oxaliplatin by RDD) and nonallergic controls (patients receiving standard oxaliplatin infusions). The primary endpoint of this study was overall survival (OS) in cases and controls (Kaplan-Meier method with log-rank test comparisons). RESULTS: OS was 23.7 months (95%CI, 15.3-30.9) for the 67 cases who underwent 337 RDDs, while for controls (n=143), OS was 34.5 months (95%CI, 21.7-55.5). There were no significant differences between the groups (HR, 1.42; 95%CI, 0.93-2.17; P =.104). CONCLUSIONS: Survival outcomes of oxaliplatin-hypersensitive patients who received oxaliplatin via RDD did not differ significantly from those of control patients who received oxaliplatin via standard administration. Receiving oxaliplatin by means of RDD might be an effective therapeutic alternative for oxaliplatin-hypersensitive patients

ANTECEDENTES: Las reacciones de hipersensibilidad al oxaliplatino podrían afectar al pronóstico vital cuando fuerzan a los pacientes a cambiar de tratamiento o cuando impiden que lo finalicen. La desensibilización rápida medicamentosa permite que estos pacientes reciban sus tratamientos de primera elección. Sin embargo, no existen datos sobre si la desensibilización rápida medicamentosa podría tener algún efecto sobre la eficacia del oxaliplatino. OBJETIVO: El objetivo de este estudio es evaluar los efectos que la desensibilización rápida medicamentosa al oxalipatlino pudiera tener sobre la eficacia del tratamiento en los pacientes alérgicos al oxaliplatino sometidos a desensibilización. MÉTODOS: Estudio retrospectivo comparando datos de supervivencia, durante un periodo de 7 años, de pacientes alérgicos al oxaliplatino (recibiendo oxaliplatino mediante desensibilización rápida medicamentosa) y controles no alérgicos (recibiendo administraciones estándar de oxaliplatino). La supervivencia global se seleccionó como el criterio de valoración de la eficacia principal y se analizó con el estimador Kaplan-Meier utilizando comparaciones mediante la prueba de log-ran. RESULTADOS: La supervivencia global de los 67 casos fue de 23,7 meses (IC95%, 15,3-30,9), que se sometieron a 337 desensibilizaciones rápidas medicamentosas. Para los 143 controles la supervivencia global fue 34,5 meses (IC95%, 21,7-55,5). No se encontraron diferencias significativamente estadísticas entre ambos grupos (HR, 1,42; IC95%, 0,93-2,17;P=0,104). CONCLUSIONES: Los resultados de supervivencia de los pacientes sometidos a desensibilización no fueron significativamente distintos a los de los controles que recibieron oxaliplatino de forma estándar. La desensibilización se presenta como una alternativa para recibir oxaliplatino de forma eficaz en pacientes alérgicos

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

BACKGROUND: Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS: Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS: Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS: The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION: This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.

Hypersensitivity and desensitization to antineoplastic agents: outcomes of 189 procedures with a new short protocol and novel diagnostic tools assessment.

BACKGROUND: Desensitization to antineoplastic agents is becoming a standard of care. Efforts to establish and improve these techniques are being made at many institutions. Our aims are to evaluate a new rapid desensitization protocol designed to be shorter (approximately 4 h) and safer (reducing hazardous drugs exposure risks) and to assess the oxaliplatin-specific immunoglobulin E (IgE) as a novel diagnostic tool. METHODS: Prospective, observational, longitudinal study with patients who, for a 1-year period, suffered reactions to antineoplastic agents and were referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were included or excluded as desensitization candidates after anamnesis, skin testing, risk assessment, and graded challenge. Specific IgE was determined in oxaliplatin-reactive patients. Candidate patients were desensitized using the new RCUH rapid desensitization protocol. RESULTS: Of 189 intravenous rapid desensitizations, 188 were successfully accomplished in the 23 patients who met inclusion criteria for desensitization (of 58 referred patients). No breakthrough reactions occurred in 94% of desensitizations, and most breakthrough reactions were mild. In 10 oxaliplatin-reactive patients, 38 desensitizations were successfully accomplished. Sensitivity for oxaliplatin-specific IgE was 38% (0.35UI/l cutoff point) and 54% (0.10UI/l cutoff point); specificity was 100% for both cutoff points. CONCLUSIONS: In the hands of a Desensitization Program, managed by drug desensitization experts, this new protocol has proven an effective therapeutic tool for hypersensitivity to several antineoplastic agents (oxaliplatin, carboplatin, paclitaxel, docetaxel, cyclophosphamide, and rituximab); moreover, it improves safety handling of hazardous drugs. We report the first large series of oxaliplatin desensitizations. Oxaliplatin-specific IgE determination could be helpful.