Dúvidas...
Depois de 9 ciclos de Temodal e de um progressão do tumor,levámos a minha mãe a dois centros de renome espanhois. Um deles indicou por ordem de preferência os seguintes tratamentos:
(não estou a prescrever...)
1- IRINOTECAN (teve de se abdicar da associação ao avastin porque a minha mãe sofre de coagulopatia)
2-CETUXIMAB
3-IMATINIB+HIDROXIUREA
Em seguida vou transcrever os resumos dos artigos que sustentaram estas prescrições, para que possamos ver as doses:
1- IRINOTECAN:
(citando)
"1: Cancer. 2003 May 1;97(9 Suppl):2381-6. Links
Two studies evaluating irinotecan treatment for recurrent malignant glioma using an every-3-week regimen.Cloughesy TF, Filka E, Kuhn J, Nelson G, Kabbinavar F, Friedman H, Miller LL, Elfring GL.
Henry Singleton Brain Cancer Research Program, UCLA School of Medicine, Los Angeles, California 90095, USA. tcloughesy@mednet.ucla.edu
Two studies were performed to evaluate the safety, tolerability, and efficacy of irinotecan (CPT-11) in the treatment of adults with malignant glioma. Patients with progressive or recurrent malignant gliomas were enrolled. In the first study, CPT-11 was administered once every 3 weeks as a 90-minute intravenous infusion at a dose of 300 mg/m(2). After 2 treatments, doses were increased to 350 mg/m(2) in those patients without Grade 3/4 toxicities. Dose modifications were made for toxicities. All 14 patients who enrolled (11 males and 3 females) were treated with CPT-11 and were assessable for survival, response, and toxicity. The majority of patients (86%) had prior surgery. Two patients had a confirmed partial response (PR), and 2 patients (14%) had stable disease (SD). Median survival was 24 weeks; median time to tumor progression (TTP) was 6 weeks. The primary hematologic toxicity was Grade 3/4 neutropenia, which was observed in 14% of patients. Infrequent Grade 3/4 nonhematologic toxicity was observed, possibly due to the concomitant use of anticonvulsants that might have altered pharmacokinetics. The second study evaluated the potential underdosing observed in patients who did or did not receive enzyme-inducing antiepileptic drugs (EIAED) by implementing an intrapatient dose escalation design. In this open-label study, treatment of patients with recurrent malignant glioma (rMG) was started at 300-400 mg/m(2) of CPT-11 every 3 weeks and, depending on individual safety and efficacy evaluation, escalated by steps of 100 mg/m(2) in subsequent courses. Thirty-five patients (median age, 43 years; gender, 11F and 24M; histology, 26 glioblastoma multiforme and 9 anaplastic glioma) have completed at least two cycles of chemotherapy and are evaluable for toxicity and response. Dose-limiting toxicity (DLT) was reached in 12 patients at doses ranging from 400-1700 mg/m(2). Preliminary efficacy data show that 3 patients exhibited PR and 15 patients exhibited SD. Median TTP was 2.7 months, and median survival was 8.5 months. Patients who did not receive anticonvulsants achieved higher peak concentrations, relative to dose, of the active metabolite SN-38 than did patients in the EIAED group. This study confirmed the activity of CPT-11 in malignant glioma and indicated that the maximum tolerated dose (MTD) for patients with rMG was considerably higher than expected but still possessed significant variability. A higher level of efficacy for CPT-11 may be observed if an MTD can efficiently be established for each patient. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11236
PMID: 12712460 [PubMed - indexed for MEDLINE]"
2- CETUXIMAB
"1: Cancer Biol Ther. 2006 Aug;5(8):912-4. Epub 2006 Aug 23. Related Articles, Links
Comment in:
Cancer Biol Ther. 2006 Sep;5(9):1242-3.
Long term responses with cetuximab therapy in glioblastoma multiforme.
Belda-Iniesta C, Carpeno Jde C, Saenz EC, Gutierrez M, Perona R, Baron MG.
Translational Oncology Unit CSIC-UAM, Medical Oncology Division, Hospital Universitario La Paz, Universidad Autonoma de Madrid, Madrid, Spain. cbelda@iib.uam.es
Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.
Publication Types:
Case Reports
PMID: 16929166 [PubMed - indexed for MEDLINE]"
3- IMATINIB+HIDROXIUREA
"Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.Reardon DA, Egorin MJ, Quinn JA, Rich JN, Gururangan S, Vredenburgh JJ, Desjardins A, Sathornsumetee S, Provenzale JM, Herndon JE 2nd, Dowell JM, Badruddoja MA, McLendon RE, Lagattuta TF, Kicielinski KP, Dresemann G, Sampson JH, Friedman AH, Salvado AJ, Friedman HS.
Department of Medicine, Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. reard003@mc.duke.edu
PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.
PMID: 16361636 [PubMed - indexed for MEDLINE]"
A decisão terapeútica aqui no hospital onde a minha mãe vai receber o tratamento escolheu a terceira opção. A minha questão é, porquê? Vejamos os argumentos que me foram dados:
1 - irinotecan (CPT11) - a oncologista diz que as doses propostas são arrasadoras para a medula ossea
2 - Cetuximab (erbitux) - a oncologista recusou este porque diz que dá muito toxidade cutanea
3 - Imatinib (Gleelvec) + Hydroxiurea - foi o tratamento escolhido pela equipa terapêutica - razão da escolha - permite uma melhor qualidade de vida.
Não tenho muita experiência, nem conhecimentos médicos mas da simples leitura dos resumos acima tenho dúvidas sobre se esta é a melhor escolha... Alguma ideia???
Minha mãe está piorando muito... precisa de algo rápido e agressivo...
(não estou a prescrever...)
1- IRINOTECAN (teve de se abdicar da associação ao avastin porque a minha mãe sofre de coagulopatia)
2-CETUXIMAB
3-IMATINIB+HIDROXIUREA
Em seguida vou transcrever os resumos dos artigos que sustentaram estas prescrições, para que possamos ver as doses:
1- IRINOTECAN:
(citando)
"1: Cancer. 2003 May 1;97(9 Suppl):2381-6. Links
Two studies evaluating irinotecan treatment for recurrent malignant glioma using an every-3-week regimen.Cloughesy TF, Filka E, Kuhn J, Nelson G, Kabbinavar F, Friedman H, Miller LL, Elfring GL.
Henry Singleton Brain Cancer Research Program, UCLA School of Medicine, Los Angeles, California 90095, USA. tcloughesy@mednet.ucla.edu
Two studies were performed to evaluate the safety, tolerability, and efficacy of irinotecan (CPT-11) in the treatment of adults with malignant glioma. Patients with progressive or recurrent malignant gliomas were enrolled. In the first study, CPT-11 was administered once every 3 weeks as a 90-minute intravenous infusion at a dose of 300 mg/m(2). After 2 treatments, doses were increased to 350 mg/m(2) in those patients without Grade 3/4 toxicities. Dose modifications were made for toxicities. All 14 patients who enrolled (11 males and 3 females) were treated with CPT-11 and were assessable for survival, response, and toxicity. The majority of patients (86%) had prior surgery. Two patients had a confirmed partial response (PR), and 2 patients (14%) had stable disease (SD). Median survival was 24 weeks; median time to tumor progression (TTP) was 6 weeks. The primary hematologic toxicity was Grade 3/4 neutropenia, which was observed in 14% of patients. Infrequent Grade 3/4 nonhematologic toxicity was observed, possibly due to the concomitant use of anticonvulsants that might have altered pharmacokinetics. The second study evaluated the potential underdosing observed in patients who did or did not receive enzyme-inducing antiepileptic drugs (EIAED) by implementing an intrapatient dose escalation design. In this open-label study, treatment of patients with recurrent malignant glioma (rMG) was started at 300-400 mg/m(2) of CPT-11 every 3 weeks and, depending on individual safety and efficacy evaluation, escalated by steps of 100 mg/m(2) in subsequent courses. Thirty-five patients (median age, 43 years; gender, 11F and 24M; histology, 26 glioblastoma multiforme and 9 anaplastic glioma) have completed at least two cycles of chemotherapy and are evaluable for toxicity and response. Dose-limiting toxicity (DLT) was reached in 12 patients at doses ranging from 400-1700 mg/m(2). Preliminary efficacy data show that 3 patients exhibited PR and 15 patients exhibited SD. Median TTP was 2.7 months, and median survival was 8.5 months. Patients who did not receive anticonvulsants achieved higher peak concentrations, relative to dose, of the active metabolite SN-38 than did patients in the EIAED group. This study confirmed the activity of CPT-11 in malignant glioma and indicated that the maximum tolerated dose (MTD) for patients with rMG was considerably higher than expected but still possessed significant variability. A higher level of efficacy for CPT-11 may be observed if an MTD can efficiently be established for each patient. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11236
PMID: 12712460 [PubMed - indexed for MEDLINE]"
2- CETUXIMAB
"1: Cancer Biol Ther. 2006 Aug;5(8):912-4. Epub 2006 Aug 23. Related Articles, Links
Comment in:
Cancer Biol Ther. 2006 Sep;5(9):1242-3.
Long term responses with cetuximab therapy in glioblastoma multiforme.
Belda-Iniesta C, Carpeno Jde C, Saenz EC, Gutierrez M, Perona R, Baron MG.
Translational Oncology Unit CSIC-UAM, Medical Oncology Division, Hospital Universitario La Paz, Universidad Autonoma de Madrid, Madrid, Spain. cbelda@iib.uam.es
Glioblastoma multiforme (GBM) is responsible for most of the deaths associated with primary brain tumors. Standard treatment includes maximal surgical resection followed by chemotherapy and concomitant radiotherapy. Most patients, however, recur shortly after treatment. Second line treatment has little efficacy and the majority of patients die soon from the disease. Recent advances in molecular biology have implicated the epidermal growth factor receptor (EGFR) signaling pathways in the progression and resistance to standard therapies for GBM. This has prompted the evaluation of EGFR tyrosine- kinase inhibitors with encouraging results. Cetuximab is a monoclonal antibody targeted against the extra cellular domain of the EGFR with activity against different tumor types, either alone or in combination with chemotherapy and/or radiation therapy. Here we describe three patients with recurrent, heavily pretreated, EGFR expressing GBM who responded to treatment with single agent cetuximab.
Publication Types:
Case Reports
PMID: 16929166 [PubMed - indexed for MEDLINE]"
3- IMATINIB+HIDROXIUREA
"Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.Reardon DA, Egorin MJ, Quinn JA, Rich JN, Gururangan S, Vredenburgh JJ, Desjardins A, Sathornsumetee S, Provenzale JM, Herndon JE 2nd, Dowell JM, Badruddoja MA, McLendon RE, Lagattuta TF, Kicielinski KP, Dresemann G, Sampson JH, Friedman AH, Salvado AJ, Friedman HS.
Department of Medicine, Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. reard003@mc.duke.edu
PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.
PMID: 16361636 [PubMed - indexed for MEDLINE]"
A decisão terapeútica aqui no hospital onde a minha mãe vai receber o tratamento escolheu a terceira opção. A minha questão é, porquê? Vejamos os argumentos que me foram dados:
1 - irinotecan (CPT11) - a oncologista diz que as doses propostas são arrasadoras para a medula ossea
2 - Cetuximab (erbitux) - a oncologista recusou este porque diz que dá muito toxidade cutanea
3 - Imatinib (Gleelvec) + Hydroxiurea - foi o tratamento escolhido pela equipa terapêutica - razão da escolha - permite uma melhor qualidade de vida.
Não tenho muita experiência, nem conhecimentos médicos mas da simples leitura dos resumos acima tenho dúvidas sobre se esta é a melhor escolha... Alguma ideia???
Minha mãe está piorando muito... precisa de algo rápido e agressivo...
posted by Carol at
1:11 da manhã
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