- Email: [email protected]
In Reply to Brown et al
Volume 94 Number 1 2016
Comments
211
4. Bernhard EJ, Mitchell JB, Deen D, et al. Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. Cancer Res 2000;60:86-91. 5. Rockwell S, Donnelly ET, Liu Y, et al. Preliminary studies of the effects of gadolinium texaphyrin on the growth and radiosensitivity of EMT6 cells in vitro. Int J Radiat Oncol Biol Phys 2002;54:536-541. 6. Donnelly ET, Liu Y, Paul TK, et al. Effects of motexafin gadolinium on DNA damage and X-rayeinduced DNA damage repair, as assessed by the comet assay. Int J Radiat Oncol Biol Phys 2005;62:1176-1186. 7. Xu S, Zakian K, Thaler H, et al. Effects of motexafin gadolinium on tumor metabolism and radiation sensitivity. Int J Radiat Oncol Biol Phys 2001;49:1381-1390. 8. Magda D, Lepp C, Gerasimchuk N, et al. Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species. Int J Radiat Oncol Biol Phys 2001; 51:1025-1036. 9. Liu FF, Okunieff P, Bernhard EJ, et al. Lessons learned from radiation oncology clinical trials. Clin Cancer Res 2013;19:6089-6100. 10. Toniatti C, Jones P, Graham H, et al. Oncology drug discovery: Planning a turnaround. Cancer Discov 2014;4:397-404.
acknowledge that this was a phase 1/2 trial, something that is exploratory by its very nature and designdand hence the title “Phase 1/2 Trials of Temozolomide, Motexafin Gadolinium, and 60-Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme: Final Results of RTOG 0513” (1). We and our patients share the commenters’ frustration when initial clinical trials fail to be the “home run” all involved wished them to be before their initiation, but we stand by our statements in the article.
In Reply to Brown et al
1. Brachman DG, Pugh SL, Ashby LS, et al. Phase 1/2 trials of temozolomide, motexafin gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: Final results of RTOG 0513. Int J Radiat Oncol Biol Phys 2015;91:961-967. 2. Brown M, Bernhard E, Mitchel J, Stone H. In regard to Brachman et al. Int J Radiat Oncol Biol Phys 2015;94:210-211. 3. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996. 4. Hashemy SI, Ungerstedt JS, Zahedi Avval F, et al. Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J Biol Chem 2006;281:10691-10697. 5. Lecane PS, Karaman MW, Sirisawad M, et al. Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res 2005;65:11676-11688. 6. Magda D, Lecane P, Miller RA, et al. Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines. Cancer Res 2005;65: 3837-3845. 7. De Stasio G, Rajesh D, Ford JM, et al. Motexafin- gadolinium taken up in-vitro by at least 90% of glioblastoma cell nuclei. Clin Cancer Res 2006;12:206-213. 8. Mehta MP, Rodrigus P, Terhaard CH, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and wholebrain radiation therapy in brain metastases. J Clin Oncol 2003;21: 2529-2536. 9. Ford JM, Seiferheld W, Alger JR, et al. Results of the phase I doseescalating study of motexafin gadolinium with standard radiotherapy in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2007;69:831-838. 10. Bernhard EJ, Mitchell JB, Deen D, et al. Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. Cancer Res 2000;60:86-91.
To the Editor: Thank you for the opportunity to respond to the comment on our article (1, 2). We would also like to thank the authors for their careful and thoughtful reading of our report. Their fundamental objection seems to be not with the trial’s design, execution, data handling, or any specific conclusions, but with the fact the trial was ever conducted. The last line of their first paragraph takes issue with our statement that the decision to conduct the trial was “firmly grounded.” In context, this statement referred to the totality of the rationale: the recently published benefit to the concurrent use in glioblastoma (GBM) treatment of temozolamide plus radiation therapy (the “Stupp Regimen”) (3), the logical desire to build on this progress, and the initial possible success and failures of motexafin gadolinium in preclinical (4-7) and clinical trials (8, 9) at that time. We did not cite the commenters’ specific preclinical work (10), but in their letter they point out their publication of a 6 nonGBM cell line study that found conflicting results in terms of radiosensitization when compared with prior cell culture studies (2). They do acknowledge that other reports’ data suggested radiosensitization but that they were “small and inconsistent.” They also point out that a human brain metastasis trial failed to reach a predetermined threshold for significance, a result we openly point out in our article (8). In their letter questioning the need for this trial, they omitted the promising GBM-specific preclinical and clinical data that existed at the time, including the cited works of De Stasio et al (who localized motexafin gadolinium distribution to the nucleus in human GBM cell lines) (7) and of Ford et al suggesting a survival benefit in a phase 1 GBM trial (9). They forget or misunderstand that undertaking Radiation Therapy Oncology Group (RTOG) protocol 0513 was not an investigator- or even RTOG-only decision, but that the National Cancer Institute had asked for the development of this trial though the review mechanism that existed at that time. Last, they failed to
David G. Brachman, MD Arizona Oncology Services Foundation, Phoenix, Arizona http://dx.doi.org/10.1016/j.ijrobp.2015.10.005
References
Randomized Comparison Radiation Therapy and Steroids for Plantar Fasciitis In Regard to Canyilmaz et al To the Editor: Canyilmaz et al (1) are to be commended for undertaking a randomized trial on radiation therapy (RT) versus steroid injection for plantar fasciitis. Their conclusion, that RT is superior by a considerable margin, was probably valid, but some of their methods were flawed.
Comments
211
4. Bernhard EJ, Mitchell JB, Deen D, et al. Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. Cancer Res 2000;60:86-91. 5. Rockwell S, Donnelly ET, Liu Y, et al. Preliminary studies of the effects of gadolinium texaphyrin on the growth and radiosensitivity of EMT6 cells in vitro. Int J Radiat Oncol Biol Phys 2002;54:536-541. 6. Donnelly ET, Liu Y, Paul TK, et al. Effects of motexafin gadolinium on DNA damage and X-rayeinduced DNA damage repair, as assessed by the comet assay. Int J Radiat Oncol Biol Phys 2005;62:1176-1186. 7. Xu S, Zakian K, Thaler H, et al. Effects of motexafin gadolinium on tumor metabolism and radiation sensitivity. Int J Radiat Oncol Biol Phys 2001;49:1381-1390. 8. Magda D, Lepp C, Gerasimchuk N, et al. Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species. Int J Radiat Oncol Biol Phys 2001; 51:1025-1036. 9. Liu FF, Okunieff P, Bernhard EJ, et al. Lessons learned from radiation oncology clinical trials. Clin Cancer Res 2013;19:6089-6100. 10. Toniatti C, Jones P, Graham H, et al. Oncology drug discovery: Planning a turnaround. Cancer Discov 2014;4:397-404.
acknowledge that this was a phase 1/2 trial, something that is exploratory by its very nature and designdand hence the title “Phase 1/2 Trials of Temozolomide, Motexafin Gadolinium, and 60-Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme: Final Results of RTOG 0513” (1). We and our patients share the commenters’ frustration when initial clinical trials fail to be the “home run” all involved wished them to be before their initiation, but we stand by our statements in the article.
In Reply to Brown et al
1. Brachman DG, Pugh SL, Ashby LS, et al. Phase 1/2 trials of temozolomide, motexafin gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: Final results of RTOG 0513. Int J Radiat Oncol Biol Phys 2015;91:961-967. 2. Brown M, Bernhard E, Mitchel J, Stone H. In regard to Brachman et al. Int J Radiat Oncol Biol Phys 2015;94:210-211. 3. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996. 4. Hashemy SI, Ungerstedt JS, Zahedi Avval F, et al. Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J Biol Chem 2006;281:10691-10697. 5. Lecane PS, Karaman MW, Sirisawad M, et al. Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res 2005;65:11676-11688. 6. Magda D, Lecane P, Miller RA, et al. Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines. Cancer Res 2005;65: 3837-3845. 7. De Stasio G, Rajesh D, Ford JM, et al. Motexafin- gadolinium taken up in-vitro by at least 90% of glioblastoma cell nuclei. Clin Cancer Res 2006;12:206-213. 8. Mehta MP, Rodrigus P, Terhaard CH, et al. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and wholebrain radiation therapy in brain metastases. J Clin Oncol 2003;21: 2529-2536. 9. Ford JM, Seiferheld W, Alger JR, et al. Results of the phase I doseescalating study of motexafin gadolinium with standard radiotherapy in patients with glioblastoma multiforme. Int J Radiat Oncol Biol Phys 2007;69:831-838. 10. Bernhard EJ, Mitchell JB, Deen D, et al. Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent. Cancer Res 2000;60:86-91.
To the Editor: Thank you for the opportunity to respond to the comment on our article (1, 2). We would also like to thank the authors for their careful and thoughtful reading of our report. Their fundamental objection seems to be not with the trial’s design, execution, data handling, or any specific conclusions, but with the fact the trial was ever conducted. The last line of their first paragraph takes issue with our statement that the decision to conduct the trial was “firmly grounded.” In context, this statement referred to the totality of the rationale: the recently published benefit to the concurrent use in glioblastoma (GBM) treatment of temozolamide plus radiation therapy (the “Stupp Regimen”) (3), the logical desire to build on this progress, and the initial possible success and failures of motexafin gadolinium in preclinical (4-7) and clinical trials (8, 9) at that time. We did not cite the commenters’ specific preclinical work (10), but in their letter they point out their publication of a 6 nonGBM cell line study that found conflicting results in terms of radiosensitization when compared with prior cell culture studies (2). They do acknowledge that other reports’ data suggested radiosensitization but that they were “small and inconsistent.” They also point out that a human brain metastasis trial failed to reach a predetermined threshold for significance, a result we openly point out in our article (8). In their letter questioning the need for this trial, they omitted the promising GBM-specific preclinical and clinical data that existed at the time, including the cited works of De Stasio et al (who localized motexafin gadolinium distribution to the nucleus in human GBM cell lines) (7) and of Ford et al suggesting a survival benefit in a phase 1 GBM trial (9). They forget or misunderstand that undertaking Radiation Therapy Oncology Group (RTOG) protocol 0513 was not an investigator- or even RTOG-only decision, but that the National Cancer Institute had asked for the development of this trial though the review mechanism that existed at that time. Last, they failed to
David G. Brachman, MD Arizona Oncology Services Foundation, Phoenix, Arizona http://dx.doi.org/10.1016/j.ijrobp.2015.10.005
References
Randomized Comparison Radiation Therapy and Steroids for Plantar Fasciitis In Regard to Canyilmaz et al To the Editor: Canyilmaz et al (1) are to be commended for undertaking a randomized trial on radiation therapy (RT) versus steroid injection for plantar fasciitis. Their conclusion, that RT is superior by a considerable margin, was probably valid, but some of their methods were flawed.