Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Aug;64(2):381–385. doi: 10.1038/bjc.1991.313

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas.

C R Pinkerton 1, J Groot-Loonen 1, A Barrett 1, S T Meller 1, D Tait 1, S Ashley 1, T J McElwain 1
PMCID: PMC1977493  PMID: 1892770

Abstract

Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.

Full text

PDF
381

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belasco J. B., Mitchell C. D., Rohrbaugh T., Rosenstock J. IV melphalan in children. Cancer Treat Rep. 1987 Dec;71(12):1277–1278. [PubMed] [Google Scholar]
  2. Byrne J., Mulvihill J. J., Myers M. H., Connelly R. R., Naughton M. D., Krauss M. R., Steinhorn S. C., Hassinger D. D., Austin D. F., Bragg K. Effects of treatment on fertility in long-term survivors of childhood or adolescent cancer. N Engl J Med. 1987 Nov 19;317(21):1315–1321. doi: 10.1056/NEJM198711193172104. [DOI] [PubMed] [Google Scholar]
  3. Carli M., Pastore G., Perilongo G., Grotto P., De Bernardi B., Ceci A., Di Tullio M., Madon E., Pianca C., Paolucci G. Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma. J Clin Oncol. 1988 Apr;6(4):654–658. doi: 10.1200/JCO.1988.6.4.654. [DOI] [PubMed] [Google Scholar]
  4. Carli M., Perilongo G., di Montezemolo L. C., De Bernardi B., Ceci A., Paolucci G., Pianca C., Calculli G., Di Tullio M. T., Grotto P. Phase II trial of cisplatin and etoposide in children with advanced soft tissue sarcoma: a report from the Italian Cooperative Rhabdomyosarcoma Group. Cancer Treat Rep. 1987 May;71(5):525–527. [PubMed] [Google Scholar]
  5. DeVita V. T. Dose-response is alive and well. J Clin Oncol. 1986 Aug;4(8):1157–1159. doi: 10.1200/JCO.1986.4.8.1157. [DOI] [PubMed] [Google Scholar]
  6. Donaldson S. S., Belli J. A. A rational clinical staging system for childhood rhabdomyosarcoma. J Clin Oncol. 1984 Feb;2(2):135–139. doi: 10.1200/JCO.1984.2.2.135. [DOI] [PubMed] [Google Scholar]
  7. Flamant F., Rodary C., Voute P. A., Otten J. Primary chemotherapy in the treatment of rhabdomyosarcoma in children: trial of the International Society of Pediatric Oncology (SIOP) preliminary results. Radiother Oncol. 1985 Apr;3(3):227–236. doi: 10.1016/s0167-8140(85)80031-1. [DOI] [PubMed] [Google Scholar]
  8. Hartmann O., Oberlin O., Lemerle J., Maraninchi D., Gastaut J. A., Mascret B., Sebahoun G., Carcassonne Y. Acute leukemia in two patients treated with high-dose melphalan and autologous marrow transplantation for malignant solid tumors. J Clin Oncol. 1984 Dec;2(12):1424–1425. doi: 10.1200/JCO.1984.2.12.1424. [DOI] [PubMed] [Google Scholar]
  9. Hays D. M. Soft tissue sarcomas in childhood. Front Radiat Ther Oncol. 1981;16:114–121. doi: 10.1159/000403098. [DOI] [PubMed] [Google Scholar]
  10. Hedley D. W., McElwain T. J., Millar J. L., Gordon M. Y. Acceleration of bone-marrow recovery by pre-treatment with cyclophosphamide in patients receiving high-dose melphalan. Lancet. 1978 Nov 4;2(8097):966–968. doi: 10.1016/s0140-6736(78)92529-1. [DOI] [PubMed] [Google Scholar]
  11. Horwich A., Brada M., Nicholls J., Jay G., Hendry W. F., Dearnaley D., Peckham M. J. Intensive induction chemotherapy for poor risk non-seminomatous germ cell tumours. Eur J Cancer Clin Oncol. 1989 Feb;25(2):177–184. doi: 10.1016/0277-5379(89)90005-9. [DOI] [PubMed] [Google Scholar]
  12. Houghton J. A., Cook R. L., Lutz P. J., Houghton P. J. Melphalan: a potential new agent in the treatment of childhood rhabdomyosarcoma. Cancer Treat Rep. 1985 Jan;69(1):91–96. [PubMed] [Google Scholar]
  13. Hryniuk W., Levine M. N. Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol. 1986 Aug;4(8):1162–1170. doi: 10.1200/JCO.1986.4.8.1162. [DOI] [PubMed] [Google Scholar]
  14. Kellie S. J., Kingston J. E. Ovarian failure after high-dose melphalan in adolescents. Lancet. 1987 Jun 20;1(8547):1425–1425. doi: 10.1016/s0140-6736(87)90606-4. [DOI] [PubMed] [Google Scholar]
  15. King D. R., Clatworthy H. W., Jr The pediatric patient with sarcoma. Semin Oncol. 1981 Jun;8(2):215–221. [PubMed] [Google Scholar]
  16. Kingston J. E., McElwain T. J., Malpas J. S. Childhood rhabdomyosarcoma: experience of the Children's Solid Tumour Group. Br J Cancer. 1983 Aug;48(2):195–207. doi: 10.1038/bjc.1983.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lawrence W., Jr, Gehan E. A., Hays D. M., Beltangady M., Maurer H. M. Prognostic significance of staging factors of the UICC staging system in childhood rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS-II). J Clin Oncol. 1987 Jan;5(1):46–54. doi: 10.1200/JCO.1987.5.1.46. [DOI] [PubMed] [Google Scholar]
  18. Maurer H. M., Beltangady M., Gehan E. A., Crist W., Hammond D., Hays D. M., Heyn R., Lawrence W., Newton W., Ortega J. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer. 1988 Jan 15;61(2):209–220. doi: 10.1002/1097-0142(19880115)61:2<209::aid-cncr2820610202>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  19. Metcalf D. Haemopoietic growth factors 1. Lancet. 1989 Apr 15;1(8642):825–827. doi: 10.1016/s0140-6736(89)92280-0. [DOI] [PubMed] [Google Scholar]
  20. Pizzo P. A., Triche T. J. Clinical staging in rhabdomyosarcoma: current limitations and future prospects. J Clin Oncol. 1987 Jan;5(1):8–9. doi: 10.1200/JCO.1987.5.1.8. [DOI] [PubMed] [Google Scholar]
  21. Selby P. J., Lopes N., Mundy J., Crofts M., Millar J. L., McElwain T. J. Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy. Br J Cancer. 1987 May;55(5):531–533. doi: 10.1038/bjc.1987.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Watanabe T., Takaue Y., Kawano Y., Koyama T., Huq M. A., Shimokawa T., Ninomiya T., Aga Y., Inai T., Hino M. Peripheral blood stem cell autotransplantation in treatment of childhood cancer. Bone Marrow Transplant. 1989 May;4(3):261–265. [PubMed] [Google Scholar]
  23. Watson A. R., Rance C. P., Bain J. Long term effects of cyclophosphamide on testicular function. Br Med J (Clin Res Ed) 1985 Nov 23;291(6507):1457–1460. doi: 10.1136/bmj.291.6507.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES