Chemotherapy Toxicity in BRCA Mutation Carriers Undergoing First-Line Platinum-Based Chemotherapy

Abstract

Objective. BRCA mutations are the most frequent mutations causing homologous recombination defects in epithelial ovarian cancers (EOC). Germline mutation carriers are heterozygous for the mutation and harbor one defective allele in all cells. This has been hypothesized to cause increased susceptibility to DNA damage in healthy cells as well as neoplastic ones. Our objective was to assess chemotherapy-associated toxicities in patients with epithelial ovarian cancer with and without a germline BRCA mutation. Mateials and Methods. A retrospective cohort study of patients with EOC receiving first-line platinum-based chemotherapy at a single center between 2006 and 2016. Indices of chemotoxicity, including blood counts, transfusion requirements, granulocyte colony-stimulating factor (gCSF) prescriptions, episodes of febrile neutropenia, and treatment delays were compared for BRCA mutation carriers and noncarriers.Results. A total of 90 women met the inclusion criteria, including 31 BRCA mutation carriers (34%) and 59 noncarriers (66%). Mean hemoglobin, neutrophil count, and platelet counts during treatment were comparable for the two patient groups. There was a trend toward a higher frequency of hematological events in BRCA mutation carriers (neutropenia <1500 per mL: 6% vs. 0%, p = .12; thrombocytopenia <100,000 per mL: 23% vs. 9%, p = .07), but these differences were not statistically significant. Similarly, no significant differences were found in surrogates of bone marrow toxicity such as blood transfusions, use of gCSF, episodes of febrile neutropenia, or treatment delays. Conclusion. BRCA mutation carriers and noncarriers receiving first-line platinum-based chemotherapy for EOC have similar hematologic toxicity profiles. Clinicians treating these patients can be reassured that chemotherapy dosing or schedule do not require adjustment in patients carrying BRCA mutations. The Oncologist 2019;24:e1471-e1475 Implications for Practice: Patients with ovarian cancer carrying BRCA mutations are more likely to have serous tumors and present with higher CA125 levels. Germline BRCA mutation status is not associated with increased frequency of adverse hematologic events among patients with ovarian cancer being treated with first-line platinum-based chemotherapy. Germline BRCA mutations are also not associated with more treatment delays or a lower number of courses completed in this patient population. These findings should reassure practitioners engaged in care for patients with ovarian cancer that BRCA mutation status most likely will not affect chemotherapy dosing or schedule.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey

“…30 Other retrospective investigations including 31-150 patients addressed chemotherapy toxicity in other types of gBRCA1-2pv neoplasms. [23][24][25][26][36][37][38][39] Albeit mostly not reporting information on dose-intensity or treatment duration, these series apparently confirm our findings. Patients with breast cancer receiving anthracycline-and taxane-based chemotherapy had no difference in toxicity as opposed to wild-type patients.…”

“…after the first cycle) neutropenia increased without any impact on overall grade 3-4 maximum toxicity. 24 , 36 By contrast, in patients with ovarian cancer receiving platinum-based chemotherapy, hematological toxicity was more serious among those harboring gBRCA1-2pv in the majority of series, 26 , 38 with a few exceptions in smaller surveys 23 or without separately reported data for patients receiving either intravenous or intraperitoneal platinum salts. 39 …”

“…cycle) neutropenia increased without any impact on overall grade 3-4 maximum toxicity. 24,36 By contrast, in patients with ovarian cancer receiving platinum-based chemotherapy, hematological toxicity was more serious among those harboring gBRCA1-2pv in the majority of series, 26,38 with a few exceptions in smaller surveys 23 or without separately reported data for patients receiving either intravenous or intraperitoneal platinum salts. 39 The unique data about chemotherapy toxicity in PDAC patients with gBRCA1-2pv can be derived from the phase II trial by O'Reilly and colleagues, 21 which investigated the activity of gemcitabine plus cisplatin with or without veliparib in patients with gBRCA1-2 or PALB2pv.…”

“…Indeed, it might be hypothesized that the defective allele that germline BRCA1-2pv carriers harbor in all healthy cells could lead to a partial impairment of the BRCA-related HR system and increased susceptibility to DNA damage also in non-neoplastic haploinsufficient cells, ultimately resulting in enhanced chemotherapy-related toxicity. 23 Different and controversial data are available on chemotherapy toxicity in breast and ovarian cancer patients with gBRCA1-2pv, 23 , 24 , 25 , 26 while no reports have addressed this topic in PDAC patients with gBRCA1-2pv.…”

Radiotherapy-induced Haematological and Intestinal Toxicity in Cervical Cancer

“…7 The RT area of cervical cancer covers the whole pelvic cavity, including anterior superior iliac spine and iliac spine, which are important hematopoietic organs. Chemotherapy-induced myelosuppression has been well recognized in solid tumor, [8][9][10] however, less study is focused on the role of irradiation alone in bone marrow activity especially in cervical cancer. Furthermore, the effects of RT on the degree of leukopenia is still controversial and the related factors are not fully evaluated.…”