H Ian Robins1, Jens Eickhoff1, Mark R Gilbert2, Terri S Armstrong3, Wenyin Shi4, John F De Groot3, Christopher J Schultz5, Grant K Hunter6, Egils Valeinis7, Mack Roach8, Emad F Youssef9, Luis Souhami10, Steve P Howard1, Frank S Lieberman11, James G Herman12, Peixin Zhang13, Minesh P Mehta14. 1. University of Wisconsin Hospital and Clinics, Madison. 2. National Institutes of Health Clinical Center Neuro-Oncology Branch, Bethesda, MD. 3. The University of Texas MD Anderson Cancer Center, Houston. 4. Thomas Jefferson University Hospital, Philadelphia, PA. 5. Froedtert and the Medical College of Wisconsin, Milwaukee. 6. Intermountain Medical Center, Salt Lake City, UT. 7. Pauls Stradiņš Clinical University Hospital, Riga, Latvia. 8. University of California San Francisco Medical Center-Mount Zion. 9. Saint Joseph's Hospital and Medical Center, Phoenix, AZ. 10. McGill University Health Centre, Montreal, Québec, Canada. 11. University of Pittsburgh Cancer Institute, PA. 12. Michigan Cancer Research Consortium CCOP, Lansing. 13. NRG Oncology Statistics and Data Management Center, Philadelphia, PA. 14. Baptist Hospital of Miami, FL.
Abstract
BACKGROUND: Fearing increased myelotoxicity, many practitioners adjust the body surface area (BSA)-calculated doses in obese patients. Regarding temozolomide (TMZ), a prior study suggested men with a BSA >2 m2 may experience increased toxicity; however, surprisingly, the inverse observation was noted in women, ie, BSA <2 m2 was associated with higher toxicity. To further clarify this issue, data derived from a large clinical trial were analyzed. METHODS: The incidence of grade 3 and 4 myelotoxicity in a newly diagnosed glioblastoma phase 3 trial (RTOG 0525) was statistically correlated with BMI and separately with BSA. All patients received radiation and TMZ followed by adjuvant standard dose TMZ vs dose-dense TMZ; dosing regimen-associated myelotoxicity and BMI/BSA were analyzed separately. Obesity was defined as a BMI ≥30. RESULTS: There was no statistically significant correlation between gender and BSA and the occurrence of myotoxicities. For the standard arm, surprisingly the incidence of grade 3/4 myotoxicities in patients with a BMI <30 was significantly higher than in patients with a BMI ≥30 (12% vs 1%, odds ratio [OR] 12.5, P < .001). There was no significant difference between obese and nonobese patients (BMI "cut-point" of 30) in the dose-dense arm (OR = 0.9, 95% confidence interval: 0.4-1.6). The grade hematological 3/4 toxicity rate was significantly higher in women vs men (14% vs 8%) P = .009 in spite of the lack of association between gender and BSA or BMI. CONCLUSION: TMZ dosing based on actual BSA is recommended with the caveat that woman are likely at higher toxicity risk.
BACKGROUND: Fearing increased myelotoxicity, many practitioners adjust the body surface area (BSA)-calculated doses in obese patients. Regarding temozolomide (TMZ), a prior study suggested men with a BSA >2 m2 may experience increased toxicity; however, surprisingly, the inverse observation was noted in women, ie, BSA <2 m2 was associated with higher toxicity. To further clarify this issue, data derived from a large clinical trial were analyzed. METHODS: The incidence of grade 3 and 4 myelotoxicity in a newly diagnosed glioblastoma phase 3 trial (RTOG 0525) was statistically correlated with BMI and separately with BSA. All patients received radiation and TMZ followed by adjuvant standard dose TMZ vs dose-dense TMZ; dosing regimen-associated myelotoxicity and BMI/BSA were analyzed separately. Obesity was defined as a BMI ≥30. RESULTS: There was no statistically significant correlation between gender and BSA and the occurrence of myotoxicities. For the standard arm, surprisingly the incidence of grade 3/4 myotoxicities in patients with a BMI <30 was significantly higher than in patients with a BMI ≥30 (12% vs 1%, odds ratio [OR] 12.5, P < .001). There was no significant difference between obese and nonobese patients (BMI "cut-point" of 30) in the dose-dense arm (OR = 0.9, 95% confidence interval: 0.4-1.6). The grade hematological 3/4 toxicity rate was significantly higher in women vs men (14% vs 8%) P = .009 in spite of the lack of association between gender and BSA or BMI. CONCLUSION: TMZ dosing based on actual BSA is recommended with the caveat that woman are likely at higher toxicity risk.
Authors: Terri S Armstrong; Yumei Cao; Michael E Scheurer; Elizabeth Vera-Bolaños; Rochelle Manning; Mehmet F Okcu; Melissa Bondy; Renke Zhou; Mark R Gilbert Journal: Neuro Oncol Date: 2009-12 Impact factor: 12.300
Authors: Roger Stupp; Monika E Hegi; Warren P Mason; Martin J van den Bent; Martin J B Taphoorn; Robert C Janzer; Samuel K Ludwin; Anouk Allgeier; Barbara Fisher; Karl Belanger; Peter Hau; Alba A Brandes; Johanna Gijtenbeek; Christine Marosi; Charles J Vecht; Karima Mokhtari; Pieter Wesseling; Salvador Villa; Elizabeth Eisenhauer; Thierry Gorlia; Michael Weller; Denis Lacombe; J Gregory Cairncross; René-Olivier Mirimanoff Journal: Lancet Oncol Date: 2009-03-09 Impact factor: 41.316
Authors: Mark R Gilbert; Meihua Wang; Kenneth D Aldape; Roger Stupp; Monika E Hegi; Kurt A Jaeckle; Terri S Armstrong; Jeffrey S Wefel; Minhee Won; Deborah T Blumenthal; Anita Mahajan; Christopher J Schultz; Sara Erridge; Brigitta Baumert; Kristen I Hopkins; Tzahala Tzuk-Shina; Paul D Brown; Arnab Chakravarti; Walter J Curran; Minesh P Mehta Journal: J Clin Oncol Date: 2013-10-07 Impact factor: 44.544