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The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin)

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Abstract

Malignant gliomas continue to be a significant sourceof mortality in young and middle aged adults.The introduction of new treatment strategies and multidisciplinaryapproaches has improved the outcome of patients withthese tumors only slightly. Because retinoic acid hasgrowth inhibitory activity against glioma and neuroblastoma cellsin cultures, we assessed the efficacy of all-trans-retinoicacid in the treatment of recurrent cerebral gliomas.Thirty-six patients with recurrent cerebral gliomas were enteredin the study and treated with 120 or150 mg/m2/day of all-trans-retinoic acid as a singleagent. The drug was given for 3 weeksfollowed with one week of rest. Two blocksof 4 weeks constituted one course of treatment.One (3%) of 34 evaluable patients had aminor response and 14 (41%) had stable disease.In the rest of the patients (56%), tumorscontinued to progress despite treatment. The median timeto progression of all evaluable patients was 8weeks, and for the responders was 17 weeks.The higher dose level (150 mg/m2) was associatedwith high incidence of headache, which responded todose reduction. The lower dose level was verywell tolerated, with mild, mainly dermatological toxicity.All-trans-retinoic acid as a single agent has nosignificant activity against recurrent cerebral gliomas.

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References

  1. Kornblith PL, Walker M: Chemotherapy for malignant gliomas. J Neurosurg 68: 1–17, 1992

    Google Scholar 

  2. Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Norrell HA, Owens G, Ransohoff J II, Wilson CB, Gehan EA, Strike TA: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. J Neurosurg 49: 333–343, 1992

    Google Scholar 

  3. Levin VA, Silver P, Hannigan J, Wara WM, Gutin P, Davis RL, Wilson CB: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 Final Report. Int J Radiat Oncol Biol Phys 18: 321–324, 1990

    Google Scholar 

  4. Jeremic B, Jovanovic D, Djuric LJ, Jeveremovic S, Mijatovic LJ: Advantage of post radiotherapy chemotherapy with CCNU, procarbazine, and vincristine (mPCV) over chemotherapy with VM-26 and CCNU for malignant gliomas. J Chemotherapy 4: 123–126, 1992

    Google Scholar 

  5. Yung WKA: Chemotherapy for malignant brain tumors. Curr Opin Oncol 2: 673–678, 1990

    Google Scholar 

  6. Smith MA, Parkinson DR, Cheson BD, Friedman MA: Retinoids in cancer therapy. J Clin Oncol 10: 839–864, 1992

    Google Scholar 

  7. Sporn MB, Roberts AB, Roche NS, Kagechika H, Shudo K: Mechanism of action of retinoids. J Am Acad Dermatol 15: 756–764, 1986

    Google Scholar 

  8. Rodts GE Jr, Black KL: Trans retinoic acid inhibits in vivo tumor growth of C6 glioma in rats: effect negatively influenced by nerve growth factor. Neurol Res 16: 184–186

  9. Yung WKA, Lotan D, Lee R, Steck PA: Modulation of growth and EGF receptor activity by retinoic acid in human glioma cells. Cancer Res 1989 49: 1014–1019, 1994

    Google Scholar 

  10. Melino G, Stephanou A, Annicchiarico-Petruzzelli M, Knight RA, Finazzi-Agr’o A, Lightman SL: Modulation of IGF-2 expression during growth and differentiation of human neuroblastoma cells: Retinoic acid may induce IGF-2. Neurosci Lett 151: 187–191, 1993

    Google Scholar 

  11. Kastner P, Perez A, Lutz Y, Rochette-Egly C, Gaub MP, Durand B, Lanotte M, Berger R, Chambon P: Structure, localization and transcriptional properties of two classes of retinoic acid receptor ??fusion proteins in acute promyelocytic leukemia (APL): Structural similarities with a new family of oncoproteins. EMBO J 11: 629–642, 1992

    Google Scholar 

  12. Alcalay M, Zangrilli D, Pandolfi PP, Longo L, Mencarelli A, Giacomucci A, Rocchi M, Biondi A, Rambaldi A, Lo Coco F, Diverio D, Donti E, Grignani F, Pelicci PG: Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor ??locus. Proc Natl Acad Sci 88: 1991

  13. Dennert G, Crowley C, Kouba J, Lotan R: Retinoid acid stimulation of the induction of mouse killer T-cells in allogenic and syngeneic systems. J Natl Cancer Inst 62: 89–94, 1979

    Google Scholar 

  14. Dennert G, Lotan R: Effect of retinoic acid on the immune system: Stimulation of T-killer cell induction. Eur J Immunol 8: 23–29, 1978

    Google Scholar 

  15. Rotello R, Lieberman R, Purchio A: Coordinated regulation of apoptosis and cell proliferation by transforming growth factor ?1 in cultured uterine epithelial cells. Proc Natl Acad Sci 88: 3412–3415, 1991

    Google Scholar 

  16. Claxton DF, Plunkett W Jr, Andreeff M, Deisseroth A: Retinoids and Cancer Therapy. J Natl Cancer Inst 84: 1306–1307, 1992

    Google Scholar 

  17. Chomienne C, Ballerini P, Balitrand N, Amar M, Bernard JF, Boivin P, Daniel MT, Berger R, Castaigne S, Degos L: Retinoic acid therapy for promyelocytic leukemia. Lancet 2: 746–747, 1989

    Google Scholar 

  18. Castaigne S, Chomienne C, Daniel MT, Bellarini P, Berger R, Fenaux P, Degos L: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I Clinical results. Blood 76: 1704–1709, 1990

    Google Scholar 

  19. Wang CJ, Chou MY, Lin JK: Inhibition of growth and development of the transplantable C-6 glioma cells inoculated in rats by retinoids and carotenoids. Cancer Lett 48: 135–142, 1989

    Google Scholar 

  20. Fischer I, Nolan C, Shea T: Effects of retinoic acid on expression of transformed phenotype in C6 glioma cells. Life Sciences 41: 463–470, 1987

    Google Scholar 

  21. Preis PN, Saya H, Nadashi L, Hochaus G, Levin V, Sad’ee W: Neuronal cell differentiation of human neuroblastoma cells by retinoic acid plus herbimycin-a. Cancer Res 48: 6530–6534, 1988

    Google Scholar 

  22. Rodriguez LA, Prados M, Silver P, Levin V: Re-evaluation of procarbazine for the treatment of recurrent malignant CNS tumors. Cancer 64: 2420–2425, 1989

    Google Scholar 

  23. Wilson CB, Gutin P, Boldrey EB: Single-agent chemotherapy of brain tumors. Arch Neurol 33: 709–714, 1976

    Google Scholar 

  24. Yung WKA, Mechtler L, Gleason MJ: Intravenous Carboplatin for recurrent malignant glioma: A phase II study. J Clin Oncol 9: 860–864, 1991

    Google Scholar 

  25. Yung WKA, Prados M, Levin VA, Fetell MR, Bennet J, Mahaley MS, Scalman M, Ectubanas E: Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: A phase I/II study. J Clin Oncol 9: 1945–1949, 1991

    Google Scholar 

  26. Gallagher RE, Said F, Pua I, Papenhausen PR, Paietta E, Wiernik PH: Expression of retinoic acid receptor-??mRNA in human leukemia cells with variable responsiveness to retinoic acid. Leukemia 3: 789–795, 1989

    Google Scholar 

  27. Hu L, Crowe D, Rheinwald J, Chambon P, Gudas LJ: Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res 51: 3972–3981, 1991

    Google Scholar 

  28. Smith MA, Adamson PC, Balis FM, Feusner J, Aronson L, Murphy RF, Horowitz ME, Reaman G, Hammond GD, Fenton RM: Phase I and pharmacokinetic evaluation of alltrans-retinoic acid in pediatric patients with cancer. J Clin Oncol 10: 1666–1673, 1992

    Google Scholar 

  29. Adamson PC: Pharmacokinetics of all-trans-retinoic acid: Clinical implications in acute promyelocytic leukemia. Semin Hematol 31: 14–17, 1994

    Google Scholar 

  30. Muindi JR, Young CW, Warrell RP Jr: Clinical pharmacology of all-trans retinoic acid. Leukemia 8 Suppl 3: S16–21, 1994

    Google Scholar 

  31. Lee JS, Newman RA, Lippman SM, Fossella FV, Calayag M, Raber MN, Krakoff IH, Hong WK: Phase I evaluation of All-trans retinoic acid with and without ketoconazole in adults with solid tumors. J Clin Oncol 31: 1501–1508, 1995

    Google Scholar 

  32. Miller VA, Rigas JR, Muindi JR, Tong WP, Venkatraman E, Kris MG, Warrell RP Jr: Modulation of all-trans retinoic acid pharmacokinetics by liarozole. Cancer Chemo Pharm 34: 522–526, 1994

    Google Scholar 

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Kaba, S.E., Kyritsis, A.P., Conrad, C. et al. The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin). J Neurooncol 34, 145–151 (1997). https://doi.org/10.1023/A:1005743707803

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