5/17/11. Intervalo entre cirugía y quimioterapia adyuvante en cáncer de mama Mauricio Lema Medina MD Astorga Clínica de Oncología Medellín, Colombia

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1 5/17/11 Intervalo entre cirugía y quimioterapia adyuvante en cáncer de mama Mauricio Lema Medina MD Astorga Clínica de Oncología Medellín, Colombia Cuál es el interavlo de tiempo apropiado entre cirugía y el inicio de quimioterapia adyuvante en cáncer de mama? Temario - Precedente en otros tumores - Cáncer de colon y recto - Carcinoma de ovario - Evidencia científica - Estudios retrospectivos - Estudios aleatorizados - Consenso - ASCO / NCCN - Uso habitual en estudios clínicos - Conclusiones 1

2 5/17/11 2

3 TI en cáncer de ovario TI en cáncer de ovario 3

4 TI en cáncer de ovario Larsen E. Acta Obstetricia et Gynecologica. 2009; 88: Grupo 2594 pacientes, Estadío I II, BriNsh Columbia - Canada <12 semanas Supervivencia años Supervivencia libre de 5 años < 4 semanas 84% 85% 4-8 semanas 85% 79% 8-12 semanas 89% 82% Retrospec3vo >12 semanas HR: 1.5, p=0.017 >12 semanas 78% 69% (p=0.004) Lohrisch C, et al. Impact on Survival of Time From Defini3ve Surgery to Ini3a3on of Adjuvant Chemotherapy for Early- Stage Breast Cancer. J Clin Oncol 24: Lohrisch C, et al. Impact on Survival of Time From Defini3ve Surgery to Ini3a3on of Adjuvant Chemotherapy for Early- Stage Breast Cancer. J Clin Oncol 24:

5 Lohrisch C, et al. Impact on Survival of Time From Defini3ve Surgery to Ini3a3on of Adjuvant Chemotherapy for Early- Stage Breast Cancer. J Clin Oncol 24: Lohrisch C, et al. Impact on Survival of Time From Defini3ve Surgery to Ini3a3on of Adjuvant Chemotherapy for Early- Stage Breast Cancer. J Clin Oncol 24: pacientes con cáncer de mama temprano (59% recibieron antraciclinas) Retrospec3vo <21 días n=368 >21 días n=793 Grupo Supervivencia años Supervivencia libre de 5 años <21 días 82% 70% >21 días 84% 72% Shannon C, et al. Does 3ming of adjuvant chemotherapy for early breast cancer influence survival? J Clin Oncol 21:

6 Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer PaNents With Tumors not Expressing Estrogen Receptors 1788 pacientes con cáncer de mama temprano (Con CMF) Retrospec3vo <21 días n=599 >21 días n=1189 Grupo Receptores hormonales (RH) Número de pacientes HR Intervalo de confianza del 95% Total RH ausentes RH RH p Colleoni M. Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Pa3ents With Tumors not Expressing Estrogen Receptors. J Clin Oncol 18: Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer PaNents With Tumors not Expressing Estrogen Receptors Supervivencia libre de progresión (%) Colleoni M. Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Pa3ents With Tumors not Expressing Estrogen Receptors. J Clin Oncol 18: Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer PaNents With Tumors not Expressing Estrogen Receptors Supervivencia libre de progresión (%) Colleoni M. Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Pa3ents With Tumors not Expressing Estrogen Receptors. J Clin Oncol 18:

7 The Sequencing of Chemotherapy and Radia3on Therapy a]er Conserva3ve Surgery for Early- Stage Breast Cancer 244 pacientes con carcinoma de mama, estadío I y II, tratadas con cirugía preservadora de mama (con antraciclinas) R Quimioterapia RT RT Quimioterapia n=122 n=122 Quimioterapia RT RT Quimioterapia Inicio RT Mediana en días (rango) 126 (98 185) 36 (14 234) Inicio QT Mediana en días (rango) 52 (15 119) 119 (48 179) RT: Radioterapia, QT: Quimioterapia Recht, A. et al. The Sequencing of Chemotherapy and Radia3on Therapy a]er Conserva3ve Surgery for Early- Stage Breast Cancer. N Engl J Med 1996; 334: The Sequencing of Chemotherapy and Radia3on Therapy a]er Conserva3ve Surgery for Early- Stage Breast Cancer 244 pacientes con carcinoma de mama, estadío I y II, tratadas con cirugía preservadora de mama (con antraciclinas) R Quimioterapia RT RT Quimioterapia n=122 n=122 Grupo Quimioterapia RT RT Quimioterapia p RFS@5y 69% 62% 0.17 DMFS@5y 75% 64% 0.05 OS@5y 81% 73% 0.11 RFS@5y: Supervivencia libre de recaída a 5 años, DMFS@5y: Supervivencia libre de metástasis a 5 años, OS@5y: Supervivencia global a 5 años Recht, A. et al. The Sequencing of Chemotherapy and Radia3on Therapy a]er Conserva3ve Surgery for Early- Stage Breast Cancer. N Engl J Med 1996; 334: Shannon C, et al. Does 3ming of adjuvant chemotherapy for early breast cancer influence survival? J Clin Oncol 21:

8 Shannon C, et al. Does 3ming of adjuvant chemotherapy for early breast cancer influence survival? J Clin Oncol 21: American Society of Clinical Oncology/Na3onal Comprehensive Cancer Network Quality Measures Cáncer de mama Denominador Riesgo esnmado de recurrencia en la medida Hormonoterapia Estadío I- III, >1 cm, dentro de 1 año del ER/PR posi3vo, >18 diagnósnco años Inició radioterapia dentre de 1 año del Estadío I- III diagnósnco Recibió Estadíos II- III quimioterapia Receptores adyuvante <120 hormonales nega3vo días del diagnósnco años 3% GL neganvo 9% GL posinvo Promedio 4% 1% con radioterapia Variación observada en NICCQ (%) % 60-91% American Society of Clinical Oncology/Na3onal Comprehensive Cancer Network Quality Measures. J Clin Oncol 26: Cuál es el interavlo de tiempo apropiado entre cirugía y el inicio de quimioterapia adyuvante en cáncer de mama? Pubmed: Evidencia Estudios retrospectivos muestran mejor supervivencia cuando se inicia quimioterapia <12 semanas después de la cirugía NCCN Las guías de la NCCN no especifican en forma EXPLÍCITA el intervalo de tiempo Se recomienda inicio de quimioterapia antes de 120 días después de la cirugía Page 24 Lohrisch C, et al. Impact on Survival of Time From Defini3ve Surgery to Ini3a3on of Adjuvant Chemotherapy for Early- Stage Breast Cancer. J Clin Oncol 24: American Society of Clinical Oncology/Na3onal Comprehensive Cancer Network Quality Measures. J Clin Oncol 26:

9 Sequencing of chemotherapy and radiation therapy for early breast cancer. Secuencia quimio-radioterapia OBJECTIVES: To determine the effects of different sequencing of chemotherapy and radiotherapy for women with early breast cancer. SELECTION CRITERIA: Randomised controlled trials evaluating different sequencing of chemotherapy and radiotherapy were included. DATA COLLECTION AND ANALYSIS: We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included studies. We derived odds ratios (OR) and risk ratios from the available numerical data. Hazard ratios were extracted directly from text. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments. Page 25 Hickey BE. Cochrane Database Syst Rev Oct 18;(4):CD Sequencing of chemotherapy and radiation therapy for early breast cancer. Secuencia quimio-radioterapia MAIN RESULTS: Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for survival, distant metastases or local recurrence, based on 853 randomised patients in two trials. One of these two trials (647 women) provided data on toxicity. Haematological toxicity (OR 1.43, confidence interval (CI) 1.01 to 2.03) and oesophageal toxicity (OR 1.44, CI 1.03 to 2.02) were significantly increased with concurrent therapy, and nausea and vomiting were significantly decreased (OR 0.70, CI 0.50 to 0.98). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), radiotherapy before chemotherapy was associated with a significantly increased risk of neutropenic sepsis (OR 2.96, 95% CI 1.26 to 6.98) compared with chemotherapy before radiotherapy, but other measures of toxicity were not significantly different. AUTHORS' CONCLUSIONS: The data included in this review, from three well conducted randomised trials, suggest that different methods of sequencing chemotherapy and radiotherapy do not appear to have a major effect on survival or recurrence for women with breast cancer if radiation therapy is commenced within 7 months after surgery Page 26 Hickey BE. Cochrane Database Syst Rev Oct 18;(4):CD TI en estudios importantes TAC vs FAC (1) Patients were randomly assigned to a study group within 60 days after surgery. Fin HER No especificado en informe final CALGB 9344 (2) Systemic therapy was to have begun within 84 days of the patient s last surgery. NSABP B31 No especificado en informe final CALGB 9741 (3) all chemotherapy was given intravenously, starting within 84 days from primary surgery. T-EV vs E-CMF (4) Within 6 weeks from the date of surgery, patients were randomly allocated 1. Martin M. N Engl J Med 2005; 352: Henderson C. J Clin Oncol 2003; 21: Citron ML. J Clin Oncol 2007; 21: Boccardo, F. Oncology 2010;78:

10 Phase III Randomized Study of Adjuvant Therapy Comprising Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With Versus Without Bevacizumab in Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer Has undergone definitive breast surgery within the past days, including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, lumpectomy and axillary dissection, or lumpectomy and sentinel node biopsy ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/ N063D Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing regimen (docetaxel and carboplatin) and study treatment must start concomitantly and no more than 14 days Phase III Randomized Study of Adjuvant Combination Chemotherapy Followed By Docetaxel Versus Ixabepilone in Women With Completely Resected Nonmetastatic, Poor- Prognosis Breast Cancer Must be able to begin chemotherapy no later than day 49 after the initial surgery Clinical Trial Comparing the Combination of TC Plus Bevacizumab to TC Alone and to TAC for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer The interval between the last surgery for breast cancer (treatment or staging) and randomization must be at least 28 days but no more than 84 days. CMF vs Ovarian ablation in Premenopausal women with ER+ Breast cancer In all women, randomized treatment was usually started within 4 weeks of mastectomy Cuál es el interavlo de tiempo apropiado entre cirugía y el inicio de quimioterapia adyuvante en cáncer de mama? Respuesta NO HAY EVIDENCIA CONFIABLE QUE INDIQUE QUE LA DEMORA EN EL INICIO DE LA QUIMIOTERAPIA HASTA 12 SEMANAS DESPUÉS DE LA CIRUGÍA AFECTE DESENLACES RELEVANTES. SIN EMBARGO, LAS PACIENTES CON DEMORAS SUPERIORES A DÍAS, SON EXCLUIDAS DE LOS ESTUDIOS CLÍNICOS IMPORTANTES. CONSIDERO QUE EL INTERVALO IDEAL DEBE SER INFERIOR A 90 DÍAS. Page 29 10