Genotoxicity of cisplatin and carboplatin in cultured human lymphocytes: a comparative study

Cisplatin and carboplatin are integral parts of many antineoplastic management regimens. Both platinum analogues are potent DNA alkylating agents that robustly induce genomic instability and promote apoptosis in tumor cells. Although the mechanism of action of both drugs is similar, cisplatin appears to be more cytotoxic. In this study, the genotoxic potential of cisplatin and carboplatin was compared using chromosomal aberrations (CAs) and sister-chromatid exchange (SCE) assays in cultured human lymphocytes. Results showed that cisplatin and carboplatin induced a significant increase in CAs and SCEs compared to the control group (p<0.01). Levels of induced CAs were similar in both drugs; however, the magnitude of SCEs induced by cisplatin was significantly higher than that induced by carboplatin (p<0.01). With respect to the mitotic and proliferative indices, both cisplatin and carboplatin significantly decreased mitotic index (p<0.01) without affecting the proliferative index (p>0.05). In conclusion, cisplatin was found to be more genotoxic than carboplatin in the SCE assay in cultured human lymphocytes, and that might explain the higher cytotoxicity of cisplatin.

The efficacy and safety of nedaplatin single therapy in 30 patients with platinum-resistant ovarian cancer.

e17075 Background: This study aimed to investigate the efficacy and safety of Nedaplatin single therapy for patients with platinum-resistant ovarian, tubal and primary peritoneal cancer after completing standard chemotherapy. Methods: From September 2002 to August 2016, 30 patients who were diagnosed with platinum-resistant ovarian cancer, were treated with Nedaplatin single therapy after completing all standard chemotherapy at our institution. Nedaplatin (80-100mg/m2) was adiministered intravenously on day 1 of a 28 day cycle. We retrospectively investigated the response rate, toxicities, and survival based on the use of Nedaplatin single therapy. Results: The median age was 58.5 years (23-76). The median number of prior chemotherapy regimen was 3 (1-7). The median platinum-free interval between the final use of platinum analogues and starting Nedaplatin single therapy was 9.4 months (0.9-54.9). Among 22 patients who had measurable disease, 8 (36.4%) responded partially to Nedaplatin single therapy. Seven patients (23.3%) experienced hematological toxicities of Grade 3/4. Six patients (20.0%) experienced non-hematological toxicities Grade 2. No treatment-related death occurred. The median progression-free survival was 3.2 months (0-23.3), and over all survival was 9.2 months (1.1-56.4) after treatment with Nedaplatin single therapy. Age (<70 years, p=0.017) and platinum-free interval (<6 months, p=0.013) were the prognosis factors for survival in univariate analyses. Conclusions: Nedaplatin single therapy seemed to be an effective and safe chemotherapy regimen for platinum-resistant ovarian cancer after completing standard chemotherapy.

The effect of front-line chemotherapy on overall survival in patients with malignant pleural mesothelioma.

e18560 Background: Malignant pleural mesothelioma (MPM) is a relatively rare, but aggressive tumor that causes high mortality. The major risk factor involved in the etiology is environmental and occupational exposure to asbestos. The optimal modality of therapy is controversial. Methods: The present study retrospectively evaluated the 141 patients from the database. Results: There were 80 males and 61 females with a mean age of 56 ± 1.07 years. The median survival in patients who were administered front-line chemotherapy was 17 months (95% CI: 13.19-20.81). 106 patients were administered pemetrexed-platinum combination and 35 patients were administered gemcitabine-platinum combination as front-line chemotherapy. For the patients who received pemetrexed-platinum regimen, a median of 6 cycles of chemotherapy was administered and 50 patients (47.2%) were able to receive all 6 cycles as planned. For the patients who received gemcitabine-platinum regimen, a median of 6 cycles of chemotherapy was administered and 19 patients (54.3%) were able to receive all 6 cycles. Median survival was found 16 months in the pemetrexed-platinum regimen and 26 months in the gemcitabine- platinum regimen. There was no statistically significant difference between the patients who received pemetrexed-platinum and gemcitabine-platinum regimens in terms of the median overall survival (p = 0.15). Conclusions: Results of our study suggest that chemotherapy prolongs overall survival. Survival rates in patients who received combining platinum analogues with pemetrexed or gemcitabine as front-line chemotherapy were found to be similar.

Neurotoxicity Caused by the Treatment with Platinum Analogues

Platinum agents (cisplatin, carboplatin, and oxaliplatin) are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.