Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; DNA Damage ; DNA Repair ; Humans ; Pharmaceutical Preparations ; Platinum/therapeutic use* ; Platinum Compounds/therapeutic use* ; Triple Negative Breast Neoplasms/genetics*

BACKGROUNDCombination paclitaxel and carboplatin is currently a first-line regimen for ovarian cancer. However, many patients develop tumor recurrence or drug resistance to this regimen. The study aims to investigate the effectiveness and safety of an oxaliplatin + epirubicin + ifosfamide regimen for the treatment of recurrent and drug-resistant epithelial ovarian cancer.

METHODSA retrospective analysis of 73 patients with recurrent and drug-resistant ovarian cancer was performed; 38 cases of them received oxaliplatin + epirubicin + ifosfamide regimens (IAP group), 35 patients received non-oxaliplatinbased chemotherapy regimens (control group). The therapeutic effects and side effects of the oxaliplatin + epirubicin + ifosfamide regimen were analyzed and summarized. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare progression-free and overall survival between the two groups.

RESULTSOf the 38 patients in the IAP group, 14 patients (36.84%) achieved complete remission, 12 (31.58%) achieved partial remission, 2 (5.26%) achieved stable disease and 10 (26.32%) developed progressive disease. The overall effective rate (complete or partial remission) of the IAP regime was 68.42%. While, of the 35 patients in the control group, 12 patients (34.29%) achieved complete remission, 3 (8.57%) achieved partial remission, 5 (14.29%) achieved stable disease and 15 (42.86%) developed progressive disease. The overall effective rate was 42.86%, which was lower than that in the IAP group (P = 0.035, χ(2) = 4.836). Progression-free survival was 9.5 months (0-64 months) in the IAP group vs. 3 months (0-74 months) in the non-oxaliplatin group (P = 0.014 by Kaplan-Meier survival curves; HR = 2.260; 95%CI 1.117-4.573; P = 0.023 by Cox proportional hazards regression). Median overall survival was 46 months (9-124 months) in the IAP group vs. 35 months (9-108 months) in non-oxaliplatin group (P = 0.018 by Kaplan-Meier survival curves; HR = 2.272; 95%CI 1.123-4.598; P = 0.022 by Cox proportional hazards regression). In IAP group, 15.79% (6/38) of the patients suffered grade III-IV bone marrow arrest. The main non-hematological side effects of the IAP regimen included nausea and vomiting (21.05%, 8/38), peripheral neurotoxicity (15.79%, 6/38) and hepatic or renal lesions (2.63%, 1/38). The main side effects of the two chemotherapy regimens showed no statistical difference.

CONCLUSIONThe oxaliplatin-based IAP regimen is potentially effective for salvage chemotherapy in patients with recurrent and drug-resistant ovarian cancer, with a better therapeutic effect and tolerable side effects.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Drug Resistance, Neoplasm ; Drug Therapy, Combination ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial ; drug therapy ; Organoplatinum Compounds ; therapeutic use ; Ovarian Neoplasms ; drug therapy ; Platinum ; therapeutic use ; Retrospective Studies

OBJECTIVETo evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.

METHODSPhase II study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50.5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.

RESULTSA total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0.061). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade II/III anemia (54.5%) and grade III/IV neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 (36.4%) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treat-ment-associated death.

CONCLUSIONGemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Female ; Humans ; Middle Aged ; Neoplasms, Glandular and Epithelial ; drug therapy ; Ovarian Neoplasms ; drug therapy ; Platinum Compounds ; administration & dosage ; adverse effects

DNA Repair ; genetics ; DNA-Binding Proteins ; genetics ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Endonucleases ; genetics ; Humans ; Neoplasms ; drug therapy ; genetics ; Nuclear Proteins ; genetics ; Organoplatinum Compounds ; therapeutic use ; Platinum Compounds ; therapeutic use ; Polymorphism, Single Nucleotide ; Transcription Factors ; genetics ; X-ray Repair Cross Complementing Protein 1 ; Xeroderma Pigmentosum Group D Protein ; genetics

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Esophageal Diseases ; etiology ; Esophageal Neoplasms ; drug therapy ; radiotherapy ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Particle Accelerators ; Platinum Compounds ; administration & dosage ; Radiation Injuries ; etiology ; Radiotherapy, High-Energy ; adverse effects

OBJECTIVETo evaluate the two-tier MDACC grading system for ovarian serous carcinoma by comparing with the WHO grading system, and to investigate the role of p53 immunostaining in ovarian serous carcinoma grading.

METHODS72 cases ovarian serous carcinoma of ovary were graded basing on the MDACC and WHO grading systems, respectively. Statistic analyses were made for the relationship between the data obtained from two grading systems and their clinical significance. All the cases were examined immunohistochemically by using antibody against p53 protein and the immunohistochemistry findings were analyzed with the two grading systems and clinical parameters.

RESULTSThere was a good correlation between the MDACC and WHO grading system (r=0.543, P=0.000). Neither system has a definite relationship with the disease-free survival time (P=0.170 vs. P=0.075), cytoreduction (P=0.478 vs. P=0.120), and the curative effect of platinum-based chemotherapy (P=0.418 vs. P=0.403). However, compared with the WHO grading system, MDACC grading system has a better correlation with tumor stage (P=0.041 vs. P=0.002), 3-year disease-free survival rate (P=0.077 vs. P=0.004), overall survival time (P=0.080 vs. P=0.046), and p53 immunohistochemistry results (P=0.334 vs. P=0.035). No significant difference was found between p53 immunohistochemistry results with other clinical characteristics and prognostic factors.

CONCLUSIONSCompared with the WHO system, the MDACC system showed a better prognostic value and was more likely correlated with the novel dualistic model for ovarian serous carcinogenesis. Although p53 immunostaining was valuable in assisting MDACC grading, it should be cautious to use it alone as an independent indicator in predicting the prognosis of ovarian serous carcinoma.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CA-125 Antigen ; metabolism ; Cystadenocarcinoma, Serous ; drug therapy ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Membrane Proteins ; metabolism ; Middle Aged ; Neoplasm Staging ; Ovarian Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Platinum Compounds ; administration & dosage ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism ; World Health Organization