A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG

Abstract

Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia.

Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: An exploratory study of the Gynecologic Oncology Group

“…Because an association between C-iN and improved PFS was not observed, post-progression therapy may have a greater, if as yet poorly understood, impact among neutropenic patients, but this is just conjecture. Nevertheless, these results are consistent with the observations reported by others who have noted that C-iN is positively correlated with patient outcomes in a variety of solid tumors including non-small cell lung, colorectal, gastric, breast, cervical, and ovarian cancer [11][12][13][14][15][16][17][18][19][20][21]. Shitara et al conducted a meta-analysis comprised of 9528 patients from 13 prospective and retrospective studies that evaluated neutropenia or leucopenia as a prognostic factor for survival [21].…”

“…There were no statistically significant differences in median PFS or median OS. In univariate analysis, C-iN was associated with improved PFS [20]. High baseline neutrophils (and other hematological parameters including the difference between baseline white blood cell count and neutrophils) were associated with reduced PFS.…”

“…More recently, the results of a large Gynecologic Cancer Intergroup trial (SCOTROC-4) were reported by Banerjee et al [20]. The investigators evaluated the efficacy and tolerability of intrapatient dose escalation of single agent carboplatin in a randomized trial of untreated stage IC-IV ovarian cancer.…”

“…High baseline neutrophils (and other hematological parameters including the difference between baseline white blood cell count and neutrophils) were associated with reduced PFS. The impact of C-iN on survival disappeared in multivariable analysis, leaving the authors to speculate that the baseline counts override the absolute nadir count [20]. It is difficult to extrapolate the SCOTROC-4 study population to the United States as the majority of patients in the trial were suboptimally debulked and none received combination platinum-taxane-based therapy.…”

Assessing the Value of Weekly Full Blood Counts in Patients with Gynecological Cancers Receiving Weekly Carboplatin/Paclitaxel Chemotherapy

“…In adults, perhaps the most common method is that of Calvert which describes the relationship between dose and AUC [12]. There is no evidence that increasing the AUC to above a level of 5 (using EDTA GFR estimates) or 6 (using Cockcroft-Gault calculated GFR) in ovary cancer patients results in any better responses or overall survival [13]. Having established reasonable safety with routine doses of platinum therapy, we do not 'routinely' assess nadir blood counts in these patients.…”