Quimioterapia Intraperitoneal no Tratamento do Câncer de Ovário
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O documento discute a quimioterapia intraperitoneal (QT IP) no tratamento do câncer de ovário. Estudos como GOG #104 e #114 mostraram que a QT IP melhora a sobrevida livre de doença em comparação com a quimioterapia intravenosa. O estudo GOG #172 encontrou uma redução de 16% no risco de progressão e de 29% no risco de morte para a QT IP versus intravenosa. No entanto, a QT IP também apresenta maior toxicidade.
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Semelhante a Quimioterapia Intraperitoneal no Tratamento do Câncer de Ovário
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Mais de Carlos Frederico Pinto
Mais de Carlos Frederico Pinto (20)
Quimioterapia Intraperitoneal no Tratamento do Câncer de Ovário
- 1. Dr. Carlos Frederico Pinto Serviço de Oncologia do Hospital Regional do Vale do Paraíba Instituto de Oncologia do Vale 2006 Quimioterapia Intraperitoneal no Câncer de Ovário
- 3. Distribuição Peritôneo/Plasma Droga Pico AUC Cisplatina 20 12 Carboplatina --- 18 Melphalan 93 65 Adriamicina 474 --- 5-FU 298 367 MTX 92 100 Paclitaxel --- 1,000
- 8. GOG #104 SWOG #8501 câncer de ovário EC III Stratify: < 0.5 cm > 0.5-2 cm R A N D O M I Z E cisplatina 100 mg/m 2 IV ciclofosfamida 600 mg/m 2 IV cada 21 dias x 6 cisplatina 100 mg/m 2 IP ciclofosfamida 600 mg/m 2 IV cada 21 dias x 6 Laparotomia Second look
- 9. GOG #104 Alberts et.al. NEJM Dec 1996 p=.02 41 mo 49 mo Sobrevida 36% 47% R Compl. ciclofosfamida e cisplatina INTRAVENOSO ciclofosfamida e cisplatina INTRAPERITONEAL
- 10. Consenso: GOG 104 O benefício da QT IP visto no GOG 104 não é maior que o benefício do novo agente, paclitaxel
- 11. GOG #114 câncer de ovário EC III < 1.0 cm R A N D O M I Z E cisplatina 75 mg/m 2 IV Paclitaxel 135 mg/m 2 IV cada 21 dias x 6 carboplatina AUC=9 x 2 IV então cisplatina 100 mg/m 2 IP Paclitaxel 135 mg/m 2 IV cada 21 dias x 6 Laparotomia Second look cisplatina 75 mg/m 2 IV ciclofosfamida 750mg/m 2 IV cada 21 dias x 6
- 12. GOG #114 câncer de ovário EC III < 1.0 cm R A N D O M I Z E cisplatina 75 mg/m 2 IV Paclitaxel 135 mg/m 2 IV cada 21 dias x 6 carboplatina AUC=9 x 2 IV then cisplatina 100 mg/m 2 IP Paclitaxel 135 mg/m 2 IV cada 21 dias x 6 Second look laparotomia cisplatina 75 mg/m 2 IV ciclofosfamida 750mg/m 2 IV cada 21 dias x 6 X
- 13. GOG #114 Markman et.el. JCO Feb 2001 P=.05 52.5 m 63.2 m S Global P=.01 22.5 m 27.6 m PFS IV Taxol IV cisplatina IV Carbo IV Taxol IP cisplatina
- 14. Consenso: GOG 114 TO benefício da QT IP no GOG 114 pode ser explicado pelo uso de 8 ciclos de quimioterapia, não pelo uso da via intraperitoneal (veja GOG 182)
- 15. GOG #172 Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 January 5, 2006
- 16. GOG #172 Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 câncer de ovário Ótima (<1cm) EC III Estratifica: Resíduo grosseiro 2 nd look planejado R A N D O M I Z E BRCA Analysis DNA Banking Paclitaxel 135 mg/m 2 /24h cisplatina 75 mg/m 2 cada 21 dias x 6 Paclitaxel 135 mg/m 2 /24h cisplatina 100 mg/m 2 IP D2 Paclitaxel 60 mg/m 2 IP D8 cada 21 dias x 6 Laparotomia Second look (se planejada)
- 17. Esquema de tratamento Cada 21 dias x 6 Regime 1 intravenoso Regime 2 Intraperitoneal D1: IV Paclitaxel (135mg/m 2 /24h) D2: IV cisplatina (75mg/m 2 ) D1: IV Paclitaxel (135mg/m 2 /24h) D2: IP cisplatina (100mg/m 2 ) D8: IP Paclitaxel (60mg/m 2 ) D1 IV D2 IV D1 IV D2 IP D8 IP
- 18. GOG #172: Toxicidade não hematológica Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 46% 24% GI G3/4 11% 1% Dor G3/4 17% 5% Fadiga G3/4 24% 7% Metabólico G3/4 6% 1% Renal G3/4 19% 9% Neuro G3/4 IP IV
- 19. GOG #172: Toxicidade Hematológica Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 16% 5% Infecção G3/4 12 % 4% Plaquetas G3/4 31% 14% Leucopenia G4 IP IV
- 20. Courses of Protocol Therapy by Regimen * carboplatina substititui cisplatina 170 (83%) 133 (65%) 86 (42%) 189 (90%) 174 (83%) 6 7 (3%) 12 (6%) 11 (5%) 4 (2%) 4 (2%) 5 4 (2%) 5 (2%) 10 (5%) 0 (0%) 2 (1%) 4 4 (2%) 9 (4%) 14 (7%) 6 (3%) 11 (5%) 3 6 (3%) 20 (10%) 30 (15%) 4 (2%) 9 (4%) 2 10 (5%) 21 (10%) 38 (19%) 7 (3%) 8 (4%) 1 4 (2%) 5 (2%) 16 (8%) 0 (0%) 2 (1%) 0 AT or Crossover to IV cisplatina or carboplatina* AT or Crossover to IV cisplatina Assigned Treatment (AT) AT or carboplatina* Assigned Treatment (AT) Intraperitoneal intravenoso Treatment Assignment # courses
- 21. GOG #172: Second Look Results 81 (100%) 85 (100%) Total 12 (15%) 13 (15%) Contra indicado 23 (28%) 37 (44%) Positivo 46 (57%) 35 (41%) Negativo IP IV Second Look
- 22. GOG #172: sobrevida 65.9 m 49.7 m Sobrevida global 23.8 m 18.3 m Livre de progressão Regime 2 Intraperitoneal Regime 1 intravenoso
- 23. Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 SOBREVIDA LIVRE DE RECIDIVA GOG#172
- 24. Armstrong, D. K. et al. N Engl J Med 2006;354:34-43 SOBREVIDA GLOBAL GOG#172
- 25. Risco Relativo: IP vs. IV Therapy, GOG #172 0.027 0.63-0.99 0.79 PFS 0.0076 0.54-0.94 0.71 OS p-value 95% CI Relative Risk
- 28. 2 heterogeneity (3 d.f.) = 1.0, p=0.80 PFS hazard ratios are not available from the published report on SWOG-8501 and the Taiwan study. PFS hazard ratio is not reported for the Italian study but it is calculated from the available data reported. 0.79
- 29. 2 heterogeneity (5 d.f.) = 3.1, p=0.68 Hazard ratio is not reported for the GONO study but it is calculated from the available data reported. Hazard ratio is not reported for the Greek study. 0.79
Notas do Editor
- Figure 2. Progression-free and Overall Survival. Panel A shows progression-free survival and Panel B overall survival among the 415 eligible patients with stage III ovarian cancer who were randomly assigned to treatment with intravenous paclitaxel and cisplatin or to treatment with intravenous paclitaxel, intraperitoneal cisplatin, and intraperitoneal paclitaxel. Eighty-five percent of the patients either died or were followed for five years. As shown in Panel A, treatment failed in 165 patients in the intravenous-therapy group: 153 (73 percent) had a recurrence, and 12 died without a documented recurrence. Forty-five patients in the intravenous-therapy group had no evidence of disease. Treatment failed in 149 patients in the intraperitoneal-therapy group: 134 (65 percent) had a recurrence, and 15 died without a documented recurrence. Fifty-six patients in the intraperitoneal group had no evidence of disease. As shown in Panel B, in the intravenous-therapy group, 127 patients (60 percent) died and 5 were lost to follow-up. Seventy-eight patients in the intravenous-therapy group were alive. In the intraperitoneal-therapy group, 101 patients (49 percent) died and 11 were lost to follow-up. Ninety-three patients in the intraperitoneal-therapy group were alive.
- Figure 2. Progression-free and Overall Survival. Panel A shows progression-free survival and Panel B overall survival among the 415 eligible patients with stage III ovarian cancer who were randomly assigned to treatment with intravenous paclitaxel and cisplatin or to treatment with intravenous paclitaxel, intraperitoneal cisplatin, and intraperitoneal paclitaxel. Eighty-five percent of the patients either died or were followed for five years. As shown in Panel A, treatment failed in 165 patients in the intravenous-therapy group: 153 (73 percent) had a recurrence, and 12 died without a documented recurrence. Forty-five patients in the intravenous-therapy group had no evidence of disease. Treatment failed in 149 patients in the intraperitoneal-therapy group: 134 (65 percent) had a recurrence, and 15 died without a documented recurrence. Fifty-six patients in the intraperitoneal group had no evidence of disease. As shown in Panel B, in the intravenous-therapy group, 127 patients (60 percent) died and 5 were lost to follow-up. Seventy-eight patients in the intravenous-therapy group were alive. In the intraperitoneal-therapy group, 101 patients (49 percent) died and 11 were lost to follow-up. Ninety-three patients in the intraperitoneal-therapy group were alive.