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High dose epirubicin and cyclophosphamide in breast cancer stage IIIB

Epirrubicina a altas dosis y ciclofosfamida en cáncer de mama IIIB

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Abstract

Introduction

The aim of the study was to test the combination of high-dose 4-epiadriamycin (4-epi) with cyclophosphamide in treatment-naive, stage IIIB breast cancer patients.

Material and methods

Between 1992 and 1994, 20 patients, 19 female and 1 male with locally-advanced (LA; n=9) and inflammatory (I; n=11) breast cancer were recruited. Mean age was 58 years (range 36–75 years). All patients had a Karnofsky performance status >80%. The treatment schedule was: 4-epi (120 mg/m2) and CTX (600 mg/m2) on day 1 every three weeks for three cycles. Those who achieved a complete response (CR) or a partial response (PR) underwent radical modified mastectomy, three cycles of 4-epi-cyclophosphamide (CTX), radiotherapy and tamoxifen (TMX). Patients with minor response (MR) or stable disease (SD) received hyperfractionated radiotherapy, three cycles of 4-epi-CTX and TMX.

Results

All patients were evaluable for response and survival analysis. There were 19 (95%) overall responses (OR); CR+PR:12(60%); MR:7(35%); SD:1(5%). Three of twelve (25%) patients who underwent surgery achieved a pathological complete response (PCR). In the LA group were seen 6 (66.66%) relapses and 5 (55.55%) deaths and the inflamatory group showed 5 (45.45%) relapses and 6 (54.54%) deaths. In follow-up, the median progresion free survival (PFS) of the group was 32 months (95% CI: 0–72). The patients with CR had a median of 59 months (95% CI: 12–107) compared to 20 months (95% CI: 5–35) in the patients with PR (log-rank p=0.081). Overall survival (OS) was 44 months (95% CI: 0–98), with a median of 31 months (95% CI: 24–38) for the LA patients and 44 months (95% CI: 0–93) for the I group (log-rank p=0.9822).

In general, the treatment was well tolerated, with grade 4 neutropenia in 6 (30%) patients and thrombocytopenia in 2 (10%). Nausea/vomiting grade 3–4 occurred in 4 (20%) patients and alopecia IV was 100% of patients.

Conclusions

The combination of high-dose 4-epirubicin and cyclophosphamide is safe, with a high percentage of overall response (95%), well tolerated and without cardio-toxicity.

Resumen

|Introducción

Presentamos los resultados de un estudio llevado a cabo entre 1992 y 1994, en un grupo de pacientes con cáncer de mama en estadio IIIB, tratados con 4-epiadriamicina (4-epi) a altas dosis y ciclofosfamida (CTX).

|Material y métodos

Se incluyeron 20 pacientes en estadio IIIB: localmente avanzado (LA; n=9) e inflamatorio (I; n=11); 19 mujeres y 1 hombre, con una media de edad de 58 años (rango 36–75) yperformance status Karnofsky mayor al 80%. Esquema de tratamiento: 4-epi (120 mg/m2) y CTX (600 mg/m2), día 1 cada tres semanas por tres ciclos. Las pacientes que alcanzaron respuesta completa (RC) o respuesta parcial (RP) fueron a mastectomía radical modificada, tres ciclos de 4-epi-CTX, radioterapia y tamoxifeno (TMX). Aquellas con respuesta menor (RM) o estabilización (EST) se trataron con radioterapia hiperfraccionada, tres ciclos de 4-epi-CTX y TMX.

|Resultados

Los 20 pacientes fueron valorables para análisis de respuesta y supervivencia: respuestas globales (RG):19 (95%); RC+RP:12(60%); RM:7(35%); EST:1(5%). Se intervinieron 12 pacientes con 3(25%) respuestas completas patológicas (RCP). En el grupo LA se produjeron 6 (66,66%) recidivas y 5 (55,55%) muertes y en el grupo inflamatorio 5 (45,45%) recaídas y 6 (54,54%) muertes.

La mediana de tiempo hasta la progresión (PFS) para el grupo fue de 32 meses (IC 95%: 0–72). Los pacientes con RC tuvieron una mediana de 59 meses (IC 95% 12–107) y con RP 20 meses (IC 95%: 5–35) (log-rank p=0,081). La mediana de seguimiento de la supervivencia global (SG) fue de 44 meses (IC 95%: 0–98), con una mediana de 31 meses (IC 95%: 24–38) para los LA y de 44 meses (IC 95%: 0–93) para los I (log-rank p=0,9822).

El tratamiento fue en general bien tolerado, observándose neutropenia grado 4 en 6 (30%), trombopenia en 2 (10%), emesis 3–4 en 4 (20%) y alopecia global en el 100% de los casos.

|Conclusiones

La combinación de 4-epiadriamicina a altas dosis y ciclofosfamida es segura, alcanzando un elevado porcentaje de respuestas globales (95%) con una tolerancia adecuada sin que se produjera ninguna toxicicidad cardiológica.

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Authors and Affiliations

  1. Servicio de Oncología Médica, Hospital General de Gran Canaria Dr. Negrín, Barranco de Ballena, s/n, 55020, Las Palmas de Gran Canaria, Spain

    Uriel Bohn Sarmiento, Jose Aguiar Morales & David Aguiar Bujanda

  2. Estadística. Hospital General de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

    Araceli Caballero Hidalgo

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  1. Uriel Bohn Sarmiento
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  2. Jose Aguiar Morales
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  3. David Aguiar Bujanda
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  4. Araceli Caballero Hidalgo
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Correspondence to Uriel Bohn Sarmiento.

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Sarmiento, U.B., Morales, J.A., Bujanda, D.A. et al. High dose epirubicin and cyclophosphamide in breast cancer stage IIIB. Rev Oncol 6, 347–352 (2004). https://doi.org/10.1007/BF02710064

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