Summary
A 5-day continuous infusion of vincristine (VCR; total dose 4 mg/m2) has been given as part of a high-dose chemoradiotherapy regimen with bone marrow transplantation. Evidence of neurotoxicity, such as weakness, paraesthesia and intestinal hypomotility, was evaluated prospectively in nine patients. Five patients had advanced neuroblastoma and four, relapsed sarcomas, and all had responded to initial conventional-dose therapy. VCR was combined with high-dose melphalan (180 mg/m2) and fractionated total-body irradiation. Plasma concentrations of VCR were measured by radioimmunoassay during and up to 24 h after the infusion. Serum and urine electrolytes and liver function tests were measured during VCR treatment and at regular intervals thereafter. VCR concentration at 1 h ranged from 1.8 to 10.9 (median 6.6) ng/ml, and a steady state was achieved by 13–30 h (median 16 h). Levels above 1 ng/ml were maintained throughout the 5-day period with a mean steady-state concentration of 1.7 ng/ml (range 1.3–2.15). After cessation of the infusion, serum concentrations fell to below 0.25 ng/ml within 24 h. Abdominal pain occurred in one patient, but neither constipation nor ileus was seen. In two patients severe muscle pain occurred in the lower limbs towards the end of the infusion. Significant electrolyte problems did not occur and, in particular, there was no evidence of inappropriate ADH secretion. Transient increases in liver enzymes were common but bilirubin was not elevated during the period of monitoring. This regimen allows a two-fold escalation in the dose of VCR to be administered, producing sustained high serum drug levels without major toxicity.
Similar content being viewed by others
References
Bachmann P, Philip T, Biron P, Bouffet E, Cheix F, Clavel M, Brunat-Mentigny M, Pommatan E (1983) Perfusion intraveineuse continue de vincristine à forte dose. Lyon Med 249: 153–158
Desai ZR, Van den Berg HW, Bridges JM, Shanks RG (1982) Can severe vincristine neurotoxicity by prevented? Cancer chemother Pharmacol 8: 211–214
El Saghir NS, Hawkins KA (1984) Hepatotoxicity following vincristine therapy. Cancer 54: 2006–2008
Helson L, Groshen S, Castello MA, Arenson E (1985) Constant infusion vincristine-Adriamycin in pediatric cancer Proc Int Soc Pediatr Oncol, pp 295–296
Holland JF, Scharlau C, Gailani S, Krant MJ, Olson KB, Horton J, Shnider BI, Lynch JJ, Owens A, Carbone PP, Coesky J, Grob D, Miller DP, Hall JC (1973) Vincristine treatment of advanced cancer: a cooperative study of 392 cases. Cancer Res 33: 1258–1264
Houghton JA, Williams LG, Torrance PM, Houghton PJ (1984) Determinants of intrinsic sensitivity to vinca alkaloids in xenografts of pediatric rhabdomyosarcomas. Cancer Res 44: 582–590
Jackson DV Jr, Bender RA (1979) Cytotoxic thresholds of vincristine in a murine and a human leukaemia cell line in vitro. Cancer Res 39: 4346–4349
Jackson DV, Sagar Sethi V, Spurr CL, Willard V, White DR, Richards F, Stuart JJ, Muss HB, Cooper MR, Homesley HD, Jobson VW, Castle MC (1981) Intravenous vincristine infusion: phase I trial. Cancer 48: 2559–2564
Jackson DV, Sagar Sethi V, Spurr CL, White DR, Richards F, Stuard JJ, Muss HB, Cooper MR, Castle MC (1981) Pharmacokinetics of vincristine infusion. Cancer Treat Rep 65: 1043–1048
Jackson DV, Paschold EH, Spurr CL, Muss HB, Richards F, Cooper MR, White DR, Stuart JJ, Hopkins JO, Rich R, Wells HB (1984) Treatment of advanced non-Hodgkin's lymphoma with vincristine infusion. Cancer 53: 2601–2606
Jackson DV, Case LD, Pope EK, White DR, Spurr CL, Richards F, Stuart JJ, Muss HB, Cooper MR, Black WR, Wortman JE, Herring WB, Caldwell RD, Capizzi RL (1985) Single agent vincristine by infusion in refractory multiple myeloma. J Clin Oncol 3: 1508–1512
Johnson FL, Bernstein ID, Hartmann JR, Chard RL (1973) Seizures associated with vincristine sulfate therapy. J Pediatr 82: 699–702
Kaufman IA, Kung FH, Koenig HM, Giammono ST (1976) Overdosage with vincristine. J Pediatr 89: 671–674
Philip T, Bernard JL, Zucker JM, Pinkerton R, Lutz P, Bordigoni P, Ploutier E, Robert A, Carton R, Philippe N, Philip I, Chantin F, Favrot M (1987) High-dose chemoradiotherapy with bone marrow transplantation as consolidation treatment in neuroblastoma: an unselected group of stage IV patients over 1 year of age. J Clin Oncol 5: 266–271
Pinkerton CR, Philip T, Biron P, Brunat Mentigney M (1985) Vincristine infusion with advanced, relapsed tumours. J Clin Oncol 3: 1437–1438
Pinkerton R, Philip R, Bouffet E, Lashford L, Kemshead J (1986) Autologous bone marrow transplantation in paediatric solid tumours. Clin Haematol 15: 187–203
Teale JD, Clough JM, Marks V (1977) Radioimmunoassay of vinblastine and vincristine. Br J Clin Pharmacol 4: 169
Van den Berg HW, Desai ZR, Wilson R, Kennedy G, Bridges JM, Shanks RG (1982) The pharmacokinetics of vincristine in man: reduced drug clearance associated with raised serum alkaline phosphatase and dose-limited elimination. Cancer Chemother Pharmacol 8: 215–219
Woods WG, O'Leary M, Nesbit ME (1981) Life-threatening neuropathy and hepatotoxicity in infants during induction therapy for acute lymphoblastic leukemia. J Pediatr 98: 642–645
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pinkerton, C.R., McDermott, B., Philip, T. et al. Continuous vincristine infusion as part of a high dose chemoradiotherapy regimen: drug kinetics and toxicity. Cancer Chemother. Pharmacol. 22, 271–274 (1988). https://doi.org/10.1007/BF00273423
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00273423