- Email: [email protected]
Re: Chemotherapy-related myelosuppression as a marker for survival in epithelial ovarian cancer patients
160
Letters to the Editor
Therapy-limiting grade 3–4 neuropathy, hypersensitivity reactions or thrombocytopenia occur in 2%, 0.6% and 39% following taxane-based chemotherapies, respectively [2,3]. Thus, it would be of relevance to know the number of patients who were dose-reduced or in whom either the platinum-agent or the taxane had to be discontinued due to toxicity. In addition, the overall toxicity profiles observed in the two patient cohorts with remarkably different prognoses would be of interest. In previous randomized studies, carboplatin–paclitaxel or carboplatin/docetaxel led to neutropenia in a significant number of patients [2,3]. Rocconi et al. stated that none of their patients received G-CSF and that this was an exclusion criterion for this study. Thus, it would be interesting to see the data gained in parallel in patients who received similar chemotherapy in conjunction with G-CSF support. Secondly, a statement should be made as to how the authors excluded the G-CSF use in all of their patients. Nowadays, G-CSF is often given to patients who experienced significant neutropenia during their preceding chemotherapy cycle, e.g. to patients developing agranulocytosis or neutropenia of 13/mm3 as stated in Table 2 [1]. Thus, it seems quite unlikely that none of the study patients who developed significant granulocytopenia at any point during treatment were prescribed G-CSF therapy. Rocconi et al. [1] state in their article that as the number of neutropenic episodes increased, improvements in progressionfree survival and platinum-sensitivity were demonstrated. We usually observe the opposite in the clinic. Once significant neutropenia occurs during one cycle this patient is at increased risk for significant neutropenia during all subsequent cycles of chemotherapy. Despite the use of secondary prophylactic G-CSF, treatment delay is often necessary. Thus, information about the number of delayed chemotherapy cycles is essential. It would also be of interest to know whether similar results were achieved using a different cut-off of the absolute neutrophil count (b1000/mm3 in the present investigation) [1]. In conclusion, although the associations described by Rocconi et al. are interesting, there is a substantial need for answers to the questions raised above.
Conflict of interest statement The author has no conflicts of interest to declare.
Edgar Petru Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria E-mail address: [email protected]. doi:10.1016/j.ygyno.2008.06.005
Re: Chemotherapy-related myelosuppression as a marker for survival in epithelial ovarian cancer patients “Forest for the trees” To the Editor: We would like to thank Dr. Petru for his comments and questions [1] regarding our manuscript. However, considering that the majority of his questions/concerns revolved around the lack of use of G-CSF, we believe the entire purpose of the manuscript was missed. Our main purpose was a hypothesis-generating study to determine if chemotherapy-related neutropenia could be used as a surrogate for cancer stem cell response to chemotherapy and survival. Simply, it is absolutely counterintuitive to include patients who received G-CSF in this study. This would reduce the very outcome we were measuring and “muddy the waters”. As such, inclusion of these patients would be a major confounding factor and fatal methodology flaw. Since G-CSF was an exclusion criteria, all episodes of neutropenia were treated with dose reductions and/or delay. We agree that further details on dose modifications would be useful, but unfortunately we do not have dose modification data available. In response to Dr. Petru's statement that it seemed unlikely that none of the patients received G-CSF, I would like to point out that the study period started in 1997, which was prior to our group's routine use of G-CSF. However, the data is what it is. We excluded patients who received G-CSF. Period. Dr. Petru's statement implies fabrication and is offensive to the authors. This retrospective study is simple in its design and aimed to answer a specific question. We hope that interpreted correctly, it draws attention to an important and growing area of research involving the role of tumor stem cells and their response to chemotherapy. Conflict of interest statement The author has no conflicts of interest to declare.
Reference References [1] Rocconi R, Matthews K, Kemper M, Hoskins K, Barnes M. Chemotherapyrelated myelosuppression as a marker of survival in epithelial ovarian cancer patients. Gynecol Oncol 2008;108:336–41. [2] Ozols R, Bundy B, Greer B, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 2003;21:3194–200. [3] Vasey P, Jayson G, Gabra H, et al. Phase III randomized trial of docetaxel– carboplatin versus paclitaxel–carboplatin as first-line chemotherapy for ovarian cancer. J Natl Cancer Inst 2004;96:1682–91.
[1] Petru E. Re: Chemotherapy-related myelosuppression as a marker for survival in epithelial ovarian cancer patients by Rocconi et al. Gynecol Oncol 2008;111: 159–60 (in this issue).
Rodney P. Rocconi Gynecologic Oncology, University of South Alabama, Mitchell Cancer Institute, 1 Mobile Infirmary Circle, Mobile, AL 36607, USA E-mail address: [email protected]. doi:10.1016/j.ygyno.2008.07.008
Letters to the Editor
Therapy-limiting grade 3–4 neuropathy, hypersensitivity reactions or thrombocytopenia occur in 2%, 0.6% and 39% following taxane-based chemotherapies, respectively [2,3]. Thus, it would be of relevance to know the number of patients who were dose-reduced or in whom either the platinum-agent or the taxane had to be discontinued due to toxicity. In addition, the overall toxicity profiles observed in the two patient cohorts with remarkably different prognoses would be of interest. In previous randomized studies, carboplatin–paclitaxel or carboplatin/docetaxel led to neutropenia in a significant number of patients [2,3]. Rocconi et al. stated that none of their patients received G-CSF and that this was an exclusion criterion for this study. Thus, it would be interesting to see the data gained in parallel in patients who received similar chemotherapy in conjunction with G-CSF support. Secondly, a statement should be made as to how the authors excluded the G-CSF use in all of their patients. Nowadays, G-CSF is often given to patients who experienced significant neutropenia during their preceding chemotherapy cycle, e.g. to patients developing agranulocytosis or neutropenia of 13/mm3 as stated in Table 2 [1]. Thus, it seems quite unlikely that none of the study patients who developed significant granulocytopenia at any point during treatment were prescribed G-CSF therapy. Rocconi et al. [1] state in their article that as the number of neutropenic episodes increased, improvements in progressionfree survival and platinum-sensitivity were demonstrated. We usually observe the opposite in the clinic. Once significant neutropenia occurs during one cycle this patient is at increased risk for significant neutropenia during all subsequent cycles of chemotherapy. Despite the use of secondary prophylactic G-CSF, treatment delay is often necessary. Thus, information about the number of delayed chemotherapy cycles is essential. It would also be of interest to know whether similar results were achieved using a different cut-off of the absolute neutrophil count (b1000/mm3 in the present investigation) [1]. In conclusion, although the associations described by Rocconi et al. are interesting, there is a substantial need for answers to the questions raised above.
Conflict of interest statement The author has no conflicts of interest to declare.
Edgar Petru Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria E-mail address: [email protected]. doi:10.1016/j.ygyno.2008.06.005
Re: Chemotherapy-related myelosuppression as a marker for survival in epithelial ovarian cancer patients “Forest for the trees” To the Editor: We would like to thank Dr. Petru for his comments and questions [1] regarding our manuscript. However, considering that the majority of his questions/concerns revolved around the lack of use of G-CSF, we believe the entire purpose of the manuscript was missed. Our main purpose was a hypothesis-generating study to determine if chemotherapy-related neutropenia could be used as a surrogate for cancer stem cell response to chemotherapy and survival. Simply, it is absolutely counterintuitive to include patients who received G-CSF in this study. This would reduce the very outcome we were measuring and “muddy the waters”. As such, inclusion of these patients would be a major confounding factor and fatal methodology flaw. Since G-CSF was an exclusion criteria, all episodes of neutropenia were treated with dose reductions and/or delay. We agree that further details on dose modifications would be useful, but unfortunately we do not have dose modification data available. In response to Dr. Petru's statement that it seemed unlikely that none of the patients received G-CSF, I would like to point out that the study period started in 1997, which was prior to our group's routine use of G-CSF. However, the data is what it is. We excluded patients who received G-CSF. Period. Dr. Petru's statement implies fabrication and is offensive to the authors. This retrospective study is simple in its design and aimed to answer a specific question. We hope that interpreted correctly, it draws attention to an important and growing area of research involving the role of tumor stem cells and their response to chemotherapy. Conflict of interest statement The author has no conflicts of interest to declare.
Reference References [1] Rocconi R, Matthews K, Kemper M, Hoskins K, Barnes M. Chemotherapyrelated myelosuppression as a marker of survival in epithelial ovarian cancer patients. Gynecol Oncol 2008;108:336–41. [2] Ozols R, Bundy B, Greer B, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 2003;21:3194–200. [3] Vasey P, Jayson G, Gabra H, et al. Phase III randomized trial of docetaxel– carboplatin versus paclitaxel–carboplatin as first-line chemotherapy for ovarian cancer. J Natl Cancer Inst 2004;96:1682–91.
[1] Petru E. Re: Chemotherapy-related myelosuppression as a marker for survival in epithelial ovarian cancer patients by Rocconi et al. Gynecol Oncol 2008;111: 159–60 (in this issue).
Rodney P. Rocconi Gynecologic Oncology, University of South Alabama, Mitchell Cancer Institute, 1 Mobile Infirmary Circle, Mobile, AL 36607, USA E-mail address: [email protected]. doi:10.1016/j.ygyno.2008.07.008