Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer

Abstract

There is increasing evidence of the efficacy of dose-dense therapy in the management of platinum-resistant/refractory ovarian cancer. We report our experience of extended weekly carboplatin and paclitaxel in this population group. Twenty patients with platinumresistant/refractory ovarian cancer received carboplatin AUC 3 and paclitaxel 70 mg m À2 on day 1, 8, 15 q 4 weekly for six planned cycles. Toxicity was assessed using Common Toxicity Criteria. Response was evaluated using radiological and CA125 criteria. Median age was 61 years (range 40 -74 years). Median number of prior therapies is three (range 1 -8). Response rate was 60% by radiological criteria (RECIST) and 76% by CA125 assessment. Grade 3 toxicities consisted of neutropenia (29% of patients) and anaemia (5%). One patient experienced grade 4 neutropenia. No grade 3/4 thombocytopaenia was reported. Fatigue, nausea and peripheral neuropathy were the most frequent non-hematological side effects. Median progression-free survival was 7.9 months and overall survival was 13.3 months. The dynamics of response to dose-dense therapy were as rapid as with front-line therapy within the same patient. This dose-dense regimen can be extended to at least 18 weekly cycles over 6 months and is well tolerated with high response rates in heavily pre-treated, platinum-resistant ovarian cancer. It forms a highly active and tolerable cytotoxic scaffold to which molecular-targeted therapies can be added in platinum-resistant ovarian cancer.

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

“…Previous studies have shown that shortening the treatment-free intervals between chemotherapy treatments can enhance therapeutic efficacy (15)(16)(17). We have previously shown that the complete elimination of these intervals through a continuous chemotherapy approach leads to a substantial improvement in ovarian cancer tumor suppression over intermittent administration (13,37).…”

“…Thus, the present study sought to investigate whether the lack of development of drug resistance is one of the mechanisms responsible for enhanced efficacy observed with continuous chemotherapy. Clinical trials have shown the survival benefits of shortening the length of intervals between chemotherapy treatments from 3 weeks to 1 week in ovarian cancer patients (15)(16)(17). In addition, low-dose prolonged exposure of chemotherapeutics, especially those that are cellcycle specific such as taxanes, has been shown to increase tumor cell kill (13,18,19).…”

Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

“…The 2014 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for ovarian cancer state that combination platinum-based chemotherapy is the preferred treatment following the first recurrence in platinum-sensitive patients (20)(21)(22). The guidelines also indicate that altering the schedule of PTX administration may produce secondary responses to treat platinum-resistant ovarian cancer, such as weekly single-agent PTX administration (80 mg/m 2 /week) or combined treatment with CBP (AUC 3/week) and PTX (70 mg/m 2 /week) (23,24). In 2006, Kyrgiou et al (25) used multiple-treatment meta-analysis methodologies to analyze 198 clinical trials from the previous 40 years, and observed that CBP and PTX are not only the best Table V.…”

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

“…Sharma et al report the highest incidence of persistent neutropenia, with significant dose delays (38% due to neutropenia) and an incidence of febrile neutropenia of 10% (2/20) including 1 death from neutropenic sepsis [19]. The weekly doses used however carboplatin AUC 3 and paclitaxel 70 mg were/m 2 ; one patient in our series was treated with the same dose of carboplatin AUC3 and similarly persistent neutropenia was noted.…”