A study of docetaxel weekly or every three weeks in combination with carboplatin as first line chemotherapy in epithelial ovarian cancer: Hematological and non-hematological toxicity profiles

Abstract

The purpose of this study was to compare the toxicity profiles of docetaxel administered on a weekly schedule and the standard three-week schedule in the treatment of advanced primary ovarian carcinoma. Eligible patients were treated with intravenous docetaxel (30 mg/m2) on days 1, 8 and 15, and carboplatin (AUC 5) on day 1 or with docetaxel (75 mg/m2) and carboplatin (AUC 5) on day 1; Q21 days for 6 cycles. This study was a pooled study of two primary phase II studies. A total of 108 patients received the weekly schedule and 59 patients received the three-week schedule. All patients were evaluated for toxicity. The overall response rate was 79% and the biochemical response 93% for the weekly schedule. The median overall survival rate was 35.3 months. Neutropenia was significantly more common (ANOVA; p<0.0001) in the three-week group than in the weekly group during all six courses of chemotherapy. Fever and infections were also more common in this group. Thrombocytopenia and anemia were slightly more common in the weekly group. Fatigue, epiphora, nail changes and taste disturbances were specific side-effects following weekly docetaxel. Peripheral sensory neuropathy (grade 1–2) increased with every cycle of treatment, but in a similar manner in the two groups. Grade 3–4 neuropathy was not recorded. Oral mucositis and myalgia were two side-effects associated with the three-week schedule. Nausea and vomiting, diarrhea and dyspnea were a limited problem in both groups. Cardiac toxicity was rare and did not differ between the two docetaxel schedules. The weekly administration was favored due to the lower rates of neutropenia, fever, infections, oral mucositis and myalgia. However, epiphora and nail changes were specific side-effects of the weekly treatment. Both regimens appeared to be rather well tolerated with similar compliance (66 and 70%) with regard to completion of the planned six courses of chemotherapy.

Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and Simulation Approach

“…The model‐predicted ANC time profiles during the first 4 cycles (Figure A) suggested that neutropenia following palbociclib is rapidly reversible rather than cumulative, with ANC levels recovered after the dosing period in each treatment cycle; no trend of worsening ANC over cycles was observed. In contrast, a retrospective study evaluating the chemotherapy agent docetaxel in patients with ovarian cancer showed a steady decrease in ANC levels, with no recovery between cycles, when using low‐dose docetaxel administered on a weekly basis; considerably lower ANC levels that remained low throughout the treatment course were observed when a high‐dose, 3‐week schedule of docetaxel was used . Consistent with these findings, preclinical results using an in vitro bone marrow toxicity model indicated that palbociclib‐induced bone marrow suppression occurred via induction of quiescence without apoptosis that was reversible following withdrawal of treatment.…”

Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation

“…Docetaxel (DTX) is a Food and Drug Administration (FDA)-approved anti-cancer drug derived from taxoid, which leads to cell cycle arrest and death [2, 3]. This drug is currently used as a monotherapy or as a combination therapy to treat non-small cell lung cancer (NSCLC) [4] as well as other types of cancers including gastric [5], breast [6], ovarian [7] and prostate cancers [8]. Despite the clinically meaningful benefits of DTX, the anti-mitotic effect of DTX associated with high cytotoxicity and severe adverse effects has limited its therapeutic applications in terms of dosage and duration, especially among older patients [9].…”

In�vitro study on reversal of ovarian cancer cell resistance to cisplatin by naringin via the nuclear factor-κB signaling pathway

“…Typically, symptoms do not present in the early stages of ovarian cancer, which renders it difficult to diagnose, and the majority of cases are at an advanced stage when diagnosed (9). At present, the suggested treatment methods of ovarian cancer are surgery and chemotherapy (10-13), and platinum-based agents and paclitaxel have become the first-line chemotherapeutic agents for the treatment of ovarian cancer (14,15). However, the emergence of multi-drug resistant ovarian cancer cells, on which chemotherapeutic agents are ineffective, may reduce the efficacy of chemotherapy (16).…”