Abstract
After successfully using cisplatin (30 mg/m2/day) and etoposide (150 mg/m2/day) in ten three-day courses for progressive low-grade gliomas, a subsequent protocol reduced the daily doses of cisplatin (to 25 mg) and etoposide (to 100 mg), with the objective of achieving the same response and three-year PFS rates with lower neurotoxicity and myelotoxicity. We treated 37 patients (median age 6 years); 23 had optochiasmatic tumours and nine were metastatic cases. Diagnoses were clinical in 13 cases and histological in 24, and comprised: pilocytic astrocytoma (17), ganglioglioma (3), pilomyxoid astrocytoma (2), and fibrillary astrocytoma (2). Treatment was prompted by radiological evidence of progression and/or clinical deterioration a median 18 months after the first diagnosis. After initial MRI staging, neurological and clinical examinations were performed before each chemotherapy cycle, with MRI after the first three courses and every three months thereafter. After a median 48 months, a volume reduction was appreciable in 24 cases (65%) and response was maximum 12 months after starting treatment. The three-year EFS and OS rates were 65 and 97%, respectively. Clinical, neurological, or functional improvements were seen in 26/37 cases. No children had a WBC nadir below 2,000/mm3. Audiological toxicity caused damage in 4/34 cases. The previous protocol had achieved volume reductions in 70% of cases, causing audiological damage (data updated) in 11/31 (P = 0.023), with three-year PFS and OS rates of 70 and 100%, respectively. Lower doses of cisplatin/etoposide are still effective in progressive low-grade glioma, with less acute and persistent morbidity.
Similar content being viewed by others
References
Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, Prados M, Jakacki R, Reaman G, Needles MN (1993) Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11:850–856
Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE (1997) Low-grade astrocytoma: a decade of experience at St. Jude Children’s Research Hospital. J Clin Oncol 15:2792–2799
Petronio J, Edwards MS, Prados M, Freyberger S, Rabbitt J, Silver P, Levin VA (1991) Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. J Neurosurg 74:701–708
Laithier V, Grill J, Le Deley MC, Ruchoux MM, Couanet D, Doz F, Pichon F, Rubie H, Frappaz D, Vannier JP, Babin-Boilletot A, Sariban E, Chastagner P, Zerah M, Raquin MA, Hartmann O, Kalifa C (2003) Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy—results of the first French prospective study for the French Society of Pediatric Oncology. J Clin Oncol 21:4572–4578
Lafay-Cousin L, Holm S, Qaddoumi I, Nicolin G, Bartels U, Tabori U, Huang A, Bouffet E (2005) Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer 103:2636–2642
McLaughlin ME, Robson CD, Kieran MW, Jacks T, Pomeroy SL, Cameron S (2003) Marked regression of metastatic pilocytic astrocytoma during treatment with imatinib mesylate (STI-571, Gleevec): a case report and laboratory investigation. J Pediatr Hematol Oncol 25:644–648
Massimino M, Spreafico F, Cefalo G, Riccardi R, Tesoro-Tess JD, Gandola L, Riva D, Ruggiero A, Valentini L, Mazza E, Genitori L, Di Rocco C, Navarria P, Casanova M, Ferrari A, Luksch R, Terenziani M, Balestrini MR, Colosimo C, Fossati-Bellani F (2002) High response rate to cisplatin/etoposide regimen in childhood low-grade glioma. J Clin Oncol 20:4209–4216
Gnekow AC (1995) Recommendations of the Brain Tumor Subcommittee for the reporting of trials: SIOP Brain Tumor Subcommittee—International Society of Pediatric Oncology. Med Pediatr Oncol 24:104–108
Kaplan E, Meyer P (1958) Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481
Brock PR, Bellman SC, Yeomans EC, Pinkerton CR, Pritchard J (1991) Cisplatin ototoxicity in children: a practical grading system. Med Pediatr Oncol 19:295–300
Gajjar A, Bhargava R, Jenkins JJ, Heideman R, Sanford RA, Langston JW, Walter AW, Kuttesch JF, Muhlbauer M, Kun LE (1995) Low-grade astrocytoma with neuraxis dissemination at diagnosis. J Neurosurg 83:67–71
Fernandez C, Figarella-Branger D, Girard N, Bouvier-Labit C, Gouvernet J, Paz Paredes A, Lena G (2003) Pilocytic astrocytomas in children: prognostic factors—a retrospective study of 80 cases. Neurosurgery 53:544–555
Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, Albin MG, Emnett RJ, Loeser S, Watson MA, Nagarajan R, Gutmann DH (2007) Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res 67:890–900
Fisher PG, Tihan T, Goldthwaite PT, Wharam MD, Carson BS, Weingart JD, Repka MX, Cohen KJ, Burger PC (2008) Outcome analysis of childhood low-grade astrocytomas. Pediatr Blood Cancer 51:245–250
Korshunov A, Meyer J, Capper D (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405
Pfister S, Janzarik WG, Remke M, Ernst A, Werft W, Becker N, Toedt G, Wittmann A, Kratz C, Olbrich H, Ahmadi R, Thieme B, Joos S, Radlwimmer B, Kulozik A, Pietsch T, Herold-Mende C, Gnekow A, Reifenberger G, Korshunov A, Scheurlen W, Omran H, Lichter P (2008) BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 118:1739–1749
De Carli E, Wang X, Puget S (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:2248 author reply 2249
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
Tibbetts KM, Emnett RJ, Gao F, Perry A, Gutmann DH, Leonard JR (2009) Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol 117:657–665
Gutmann DH (2008) Using neurofibromatosis-1 to better understand and treat pediatric low-grade glioma. J Child Neurol 23:1186–1194
Walker D (2003) Recent advances in optic nerve glioma with a focus on the young patient. Curr Opin Neurol 16:657–664
Emanuel PD (2008) Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Leukemia 22:1335–1342
Smith MA, Rubinstein L, Anderson JR, Arthur D, Catalano PJ, Freidlin B, Heyn R, Khayat A, Krailo M, Land VJ, Miser J, Shuster J, Vena D (1999) Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol 17:275–281
Shankar SM, Chen L, Zhou T, Krailo MD, Reaman G, Bhatia S (2008) Risk of therapy related myelodisplasia and acute myeloid leukemia (t-MDS/AML) in children exposed to alkylating agents, anthracyclines, platinum compounds and epipodophyllotoxins: a report from Children’s Oncology Grop (COG). J Clin Oncol 26 (abstr 10005)
Riva D, Massimino M, Giorgi C, Nichelli F, Erbetta A, Usilla A, Vago C, Bulgheroni S (2009) Cognition before and after chemotherapy alone in children with chiasmatic-hypothalamic tumors. J Neurooncol 92:49–56
Puget S, Crimmins DW, Garnett MR, Grill J, Oliveira R, Boddaert N, Wray A, Lelouch-Tubiana A, Roujeau T, Di Rocco F, Zerah M, Sainte-Rose C (2007) Thalamic tumors in children: a reappraisal. J Neurosurg 106(5 Suppl):354–362
Jahraus CD, Tarbell NJ (2006) Optic pathway gliomas. Pediatr Blood Cancer 46:586–596
Hug EB, Muenter MW, Archambeau JO, DeVries A, Liwnicz B, Loredo LN, Grove RI, Slater JD (2002) Conformal proton radiation therapy for pediatric low-grade astrocytomas. Strahlenther Onkol 178:10–17
Acknowledgements
This paper was presented in part at the ISPNO, 13th International Symposium on Pediatric Neuro-Oncology: June 29–July 2, 2008 Chicago, USA. This paper was partly financed by the AIRC (Associazione Italiana per la Ricerca sul Cancro) and Associazione Bianca Garavaglia (Busto Arsizio, Varese).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Massimino, M., Spreafico, F., Riva, D. et al. A lower-dose, lower-toxicity cisplatin–etoposide regimen for childhood progressive low-grade glioma. J Neurooncol 100, 65–71 (2010). https://doi.org/10.1007/s11060-010-0136-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-010-0136-6