PURPOSE: The incidence of secondary leukemia after epipodophyllotoxin treatment and the relationship between epipodophyllotoxin cumulative dose and risk are not well characterized. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of secondary leukemia after epipodophyllotoxin treatment. METHODS: Twelve NCI-supported cooperative group clinical trials were identified that use epipodophyllotoxins at low (<1.5 g/m2 etoposide), moderate (1.5 to 2.99 g/m2 etoposide), or higher (> or =3.0 g/m2 etoposide) cumulative doses. Cases of secondary leukemia (including treatment-related myelodysplastic syndrome) occurring on these trials have been reported to CTEP, as has duration of follow-up for all patients, thereby allowing calculation of cumulative 6-year incidence rates of secondary leukemia for each etoposide dose group. RESULTS: The calculated cumulative 6-year risks for development of secondary leukemia for the low, moderate, and higher cumulative dose groups were 3.3%, (95% upper confidence bound of 5.9%), 0.7% (95% upper confidence bound of 1.6%), and 2.2%, (95% upper confidence bound of 4.6%), respectively. CONCLUSION: Within the context of the epipodophyllotoxin cumulative dose range and schedules of administration encompassed by the monitoring plan regimens, and within the context of multiagent chemotherapy regimens that include alkylating agents, doxorubicin, and other agents, factors other than epipodophyllotoxin cumulative dose seem to be of primary importance in determining the risk of secondary leukemia. Data obtained by the CTEP secondary leukemia monitoring plan support the relative safety of using epipodophyllotoxins according to the therapeutic plans outlined in the monitored protocols.
PURPOSE: The incidence of secondary leukemia after epipodophyllotoxin treatment and the relationship between epipodophyllotoxin cumulative dose and risk are not well characterized. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of secondary leukemia after epipodophyllotoxin treatment. METHODS: Twelve NCI-supported cooperative group clinical trials were identified that use epipodophyllotoxins at low (<1.5 g/m2 etoposide), moderate (1.5 to 2.99 g/m2 etoposide), or higher (> or =3.0 g/m2 etoposide) cumulative doses. Cases of secondary leukemia (including treatment-related myelodysplastic syndrome) occurring on these trials have been reported to CTEP, as has duration of follow-up for all patients, thereby allowing calculation of cumulative 6-year incidence rates of secondary leukemia for each etoposide dose group. RESULTS: The calculated cumulative 6-year risks for development of secondary leukemia for the low, moderate, and higher cumulative dose groups were 3.3%, (95% upper confidence bound of 5.9%), 0.7% (95% upper confidence bound of 1.6%), and 2.2%, (95% upper confidence bound of 4.6%), respectively. CONCLUSION: Within the context of the epipodophyllotoxin cumulative dose range and schedules of administration encompassed by the monitoring plan regimens, and within the context of multiagent chemotherapy regimens that include alkylating agents, doxorubicin, and other agents, factors other than epipodophyllotoxin cumulative dose seem to be of primary importance in determining the risk of secondary leukemia. Data obtained by the CTEP secondary leukemia monitoring plan support the relative safety of using epipodophyllotoxins according to the therapeutic plans outlined in the monitored protocols.
Authors: Lynda M Vrooman; Donna S Neuberg; Kristen E Stevenson; Barbara L Asselin; Uma H Athale; Luis Clavell; Peter D Cole; Kara M Kelly; Eric C Larsen; Caroline Laverdière; Bruno Michon; Marshall Schorin; Cindy L Schwartz; Harvey J Cohen; Steven E Lipshultz; Lewis B Silverman; Stephen E Sallan Journal: Eur J Cancer Date: 2011-04-20 Impact factor: 9.162
Authors: M D Megonigal; N K Cheung; E F Rappaport; P C Nowell; R B Wilson; D H Jones; K Addya; D G Leonard; B H Kushner; T M Williams; B J Lange; C A Felix Journal: Proc Natl Acad Sci U S A Date: 2000-03-14 Impact factor: 11.205
Authors: Kerri Nottage; Jennifer Lanctot; Zhenghong Li; Joseph P Neglia; Smita Bhatia; Sue Hammond; Wendy Leisenring; Anna Meadows; Deokumar Srivastava; Leslie L Robison; Gregory T Armstrong Journal: Blood Date: 2011-04-15 Impact factor: 22.113
Authors: Peter McLaughlin; Elihu Estey; Armand Glassman; Jorge Romaguera; Felipe Samaniego; Ana Ayala; Kimberly Hayes; Anne Marie Maddox; H Alejandro Preti; Fredrick B Hagemeister Journal: Blood Date: 2005-03-01 Impact factor: 22.113
Authors: Brian H Kushner; Kim Kramer; Shakeel Modak; Li-Xuan Qin; Karima Yataghena; Suresh C Jhanwar; Nai-Kong V Cheung Journal: Pediatr Blood Cancer Date: 2009-07 Impact factor: 3.167