Gemcitabine and carboplatin treatment in Patients with relapsing ovarian cancer

Abstract

Despite progress in primary treatment of patients with advanced ovarian cancer, the majority develop recurrence of the disease. A platinum salt treatment, either as monotherapy or in combination with another cytostatic agent, is indicated for patients who have relapsed 6 or more months after primary treatment and thus have platinum-sensitive relapse. Because repeated use of paclitaxel treatment may lead to substantial neurotoxicity, the combination of gemcitabine with carboplatin represents a suitable treatment option, which is widely used in common clinical practice in the Czech Republic and Slovakia.This non-interventional, prospective study observed the effectiveness and tolerability of second-line treatment with gemcitabine and carboplatin in patients with platinum-sensitive relapse of ovarian cancer in routine clinical practice. The primary endpoint was to evaluate the survival and secondary endpoints were to evaluate time to disease progression, objective tumor response rate, and treatment toxicity.Patients were enrolled to planned second-line treatment with gemcitabine and carboplatin (gemcitabine 1000 mg/m 2 and carboplatin AUC 5 on Day 1, and gemcitabine 1000 mg/m 2 on Day 8 of a 21-day cycle) for platinum-sensitive relapse of ovarian cancer as a part of routine clinical practice and followed for 12 months. The events (death, tumor progression), tumor response, and maximal grades of toxicity were recorded according to common clinical practice. Survival time (using Kaplan-Meier analysis) and objective tumor response rate were calculated using data forms, and a subgroup analysis was performed using log rank tests for time-to-event endpoints; p-values were also calculated. Response rates were calculated for the whole population; for the subgroups, the Fisher's exact test was performed and only p-values were calculated.Between January 2004 and June 2005, 53 patients were enrolled in the study. The median age was 57 years and 96% of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 and 1 at baseline. Approximately 91% of patients were originally diagnosed with stage III or IV; 60% of patients had disease free intervals (DFIs) of 12 or more months from previous therapy, and the additional 40% less than 12 months. The 1-year survival rate was 83%. Median survival time was not determined within the 12-month period following the start of the treatment study due to the limited duration of follow-up. Objective tumour response rate was 67.3%. Most common reasons for discontinuation of therapy were "Planned treatment completed" (53%) and "Tumor progression" (11%). Most common toxicities were leukopenia, anaemia, neutropenia, and thrombocytopenia; grades 3 and 4 of these toxicity types did not exceed 30%. Febrile neutropenia was recorded in two patients. Most common non-haematological toxicities were nausea and vomiting, fatigue, and neuropathy; grades 3 and 4 of these were below 6%. Results on time to disease progression are not published due to inconsistent statistical analysis of...

Efficacy of a modified regimen of gemcitabine and cisplatin among women with recurrent epithelial ovarian cancer

“…Several regimens of that combination have been reported by various authors. [2,[15][16][17][18][19][20][21][22][29][30][31] The modified regimen we started in 2002 which entailed reducing the dose of gemcitabine and increasing the total dose of cisplatin and dividing treatment over two weeks was adopted in the hope of maximizing efficacy and reducing myelotoxicity. In addition, we used growth factor support for both white and red blood cells in lieu of reducing chemotherapy doses and in order to avoid chemotherapy delays.…”

“…Response rate PFI (months) Gemcitabine/cisplatin Nagourney et al [17] 27 52% 70% 6 Tewari et al [19] 22 100% 64% 3.9 Brewer et al [21] 57 100% 16% 5.9 Bozas et al [29] 50 100% 31.5% 4 Current study 28 18% 60.7% 7 Gemcitabine/carboplatin Papadimitriou et al [18] 43 0 40.4% 9 Pfisterer et al [2] 178 0 47.2% 8.6 Kose et al [20] 40 0 62.5% 9.6 * Sufliarsky et al [30] 53 0 67.3% Not mentioned Gemcitabine/cisplatin or carboplatin Rose et al [15] 36 100% 42.9% 6 Villella et al [16] 29 66% 55% < 6 Gemcitabine/cisplatin or carbopltin and bevacizumab Richardson et al [31] 35 20% 78% 12…”

“…Bozas et al [29] 81.5% 18.5% 96.5% 14.8% not mentioned * Sufliarsky et al [30] 22.7% 20.8% 28.4% 5.7% 60.3%…”

Synthetic isothiocyanate indole-3-ethyl isothiocyanate (homoITC) enhances sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to cisplatin

“…The anticancer effects of various chemopreventive agents [1][2][3][4][5][6]or their combinations with chemotherapeutic drugs [7][8][9][10][11] have been studied extensively.…”

“…However, frequent development of resistance to platinum-based chemotherapy limits its use and stimulates the search for combination therapy aimed at circumventing or decreasing of platinum resistance [10,23] Cellular resistance to platinum can arise by multiple mechanisms related to GSH-based detoxification and metallothionein content, ABC transporters overexpression, an increase in DNA repair capacity, but also because of aberrant properties of signal transduction pathways involved in cell cycle control and apoptosis (for example p53 alterations, Bcl-2 expression, ERK activation) [24].…”