Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers / 부인종양

OBJECTIVE: Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. METHODS: We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. RESULTS: Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m². More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). CONCLUSION: The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer / 부인종양

OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged < or =40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Evaluation of oral-motor movements and facial mimic in patients with head and neck burns by a public service in Brazil

OBJECTIVES: The purpose of this study was to analyze the characteristics of oral-motor movements and facial mimic in patients with head and neck burns. METHODS: An observational descriptive cross-sectional study was conducted with patients who suffered burns to the head and neck and who were referred to the Division of Orofacial Myology of a public hospital for assessment and rehabilitation. Only patients presenting deep partial-thickness and full-thickness burns to areas of the face and neck were included in the study. Patients underwent clinical assessment that involved an oral-motor evaluation, mandibular range of movement assessment, and facial mimic assessment. Patients were divided into two groups: G1 - patients with deep partial-thickness burns; G2 - patients with full-thickness burns. RESULTS: Our final study sample comprised 40 patients: G1 with 19 individuals and G2 with 21 individuals. The overall scores obtained in the clinical assessment of oral-motor organs indicated that patients with both second- and third-degree burns presented deficits related to posture, position and mobility of the oral-motor organs. Considering facial mimic, groups significantly differed when performing voluntary facial movements. Patients also presented limited maximal incisor opening. Deficits were greater for individuals in G2 in all assessments. CONCLUSION: Patients with head and neck burns present significant deficits related to posture, position and mobility of the oral myofunctional structures, including facial movements. .

ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.

Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3α, VEGF, survivin, and Bcl-XL, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3β. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

Hexamethylmelamine as Consolidation Treatment for Patients with Advanced Epithelial Ovarian Cancer in Complete Response after First-Line Chemotherapy

The aim of this study was to assess the efficacy of consolidation therapy with hexamethylmelamine (HMM) in patients with advanced epithelial ovarian cancer (EOC). Patients treated at our hospital between January 1997 and November 2006 and in documented clinical complete response from advanced ovarian cancer following front-line platinum-based therapy were retrospectively analyzed. The patients treated with HMM were compared to the patients of matched counterpart without consolidation therapy. Of 102 patients enrolled, 49 were treated with HMM and 53 received no consolidation treatment. For patients with HMM and observed patients, the mean age were 54.6 and 55.6 yr; the distribution of stage was similar (P=0.977); the optimal surgery was performed in 36 (73.5%) and 44 (83%) (P=0.336); the recurrence rate were 27 (55.1%) and 33 (62.3%) (P=0.463); and the median progression-free survival were 38 months and 21 months for patients with HMM and observed patients (P=0.235). No treatment-related adverse events were reported during the follow-up period. Although this study failed to show the significant survival benefit of consolidation therapy with HMM in patients with advanced EOC, we consider that our study can contribute data to investigate the effectiveness of consolidation therapy in epithelial ovarian cancer.

Efficacy of platinum plus cyclophosphamide in patients with epithelial ovarian cancer.

OBJECTIVES: To determine the response rate (RR), 5-year progression-free survival (PFS), and the 5-year survival rate (SVR) of epithelial ovarian cancer patients who received platinum plus cyclophosphamide as adjuvant postoperative chemotherapy. MATERIAL AND METHOD: Epithelial ovarian cancer patients who underwent tumor debulking surgery and received platinum plus cyclophosphamide as adjuvant chemotherapy at Vajira Hospital from January 1995 to December 2003 were identified. All clinical and pathological data were reviewed RESULTS: Among 114 patients included in the present study, 101 patients were evaluable for response. Overall response rate was 79.2%. The 5-year PFS and 5-year SVR were 60.3% (95% confidence interval [95% CI]; 50.5, 70.1%) and 60.7% (95% CI; 50.9, 70.5%) respectively. Subgroup analysis showed better RR, PFS, and SVR in early stage than advanced stage disease. CONCLUSION: The overall RR, 5-year PFS, and 5-year SVR of patients of the whole group were modest. These outcomes were significantly better in the early stage than the advanced stage.

Adverse affects of paclitaxel and carboplatin combination chemotherapy in epithelial gynecologic cancer.

OBJECTIVE: To evaluate the adverse affects of paclitaxel and carboplatin combination chemotherapy. DESIGN: Descriptive cross sectional study MATERIAL AND METHOD: Patients with epithelial cancer of the ovary, fallopian tube and peritoneum treated with paclitaxel and carboplatin combination chemotherapy at Chiang Mai University Hospital between August 2003 and August 2004. RESULTS: Of 224 evaluable cycles in 63 patients treated with paclitaxel (175 mg/m2) and carboplatin (AUC 5), grade 3 and 4 neutropenia occurred in 37.1% or 41.3% of patients. 4.8% of patients experienced febrile neutropenia. Grade 3 and 4 leukopenia occurred in 8.6% of courses and 12.6% of patients. Grade 3 anemia occurred in 5.2% of courses and 9.5% of patients. Grade 3 thrombocytopenia occurred in 2.8% of courses and 9.6% of patients. The nonhematologic adverse affects were rare, however, some adverse events may be potentially life threatening. CONCLUSION: Adverse affects of paclitaxel and carboplatin combination chemotherapy are acceptable and manageable in the majority of patients.

Epithelial-myoepithelial carcinoma of the base of tongue: pathology and management.

Epithelial-myoepithelial carcinoma is a rare tumor which makes up about 0.2% of epithelial neoplasms of the salivary glands; parotid gland being the most common primary site of origin. The tumor may also very rarely originate in minor salivary glands of the base of the tongue. Due to rarity of its occurrence, histogenesis and clear cut therapeutic guidelines are not defined. The present report describes the case of a 48 year old male who was diagnosed to have a tubular variant of epithelial-myoepithelial carcinoma of the base of tongue, Stage T3 N0 M0 (Stage group III). The patient was treated with neoadjuvant chemotherapy followed by radical radiotherapy (Rt) and is alive with no evidence of disease 14 months following end of treatment.

The use of lenograstim (Granocyte) in chemotherapy for ovarian cancer.

We have conducted an open, controlled study on the febrile neutropenia effects by Lenograstim (Granocyte) therapy following cytotoxic chemotherapy of cisplatinum and cyclophosphamide in patients with primary advanced epithelial ovarian cancer. Eligible patients (n = 17) were divided into 2 groups receiving a combined chemotherapy of intravenous cisplatinum (70 mg/m2) and cyclophosphamide (700 mg/m2) with or without the addition of Lenograstim. Subcutaneous administration of Lenograstim (100 micrograms/day) for 7 consecutive days was given from day 8 to day 14 of the 3rd to the 5th cycle of chemotherapy in Lenograstim treated patients. After 3 cycles of treatment, Lenograstim treated patients (group 1, n = 10) showed a significant improvement in white blood cell (WBC) count as compared with group 2 (control) of 7 patients (p = 0.00002). Group 1 patients also showed an increased C-reactive protein, though of no significance. There were no significant differences among the 2 groups regarding ESR, hematocrit, platelet counts and blood chemistry profiles. This preliminary data encourages more study of the benefits of Lenograstim in the treatment of ovarian cancer.

Epithelial ovarian cancer treated by platinum or platinum analogue with cyclophosphamide: experience in Ramathibodi Hospital.

This study presented the outcome of 92 EOC patients treated by platinum or platinum analogue with cyclophosphamide from January 1, 1993 to December 31, 1995. There were 77 evaluable patients. The follow-up ranged from 4-42 months (median 14 months). The over all 3-year survival was 64 per cent and the median progression-free interval was 16 months for the whole group. There was no significant difference in survival between patients who received cisplatin and those who received carboplatin (P = 0.093). Patients who underwent optimal debulking surgery had significantly longer progression-free interval (P = 0.001) than those who had sub-optimal surgery. Fifty four per cent of patients with clear cell carcinoma died of the disease. Patients who received cisplatin had a drop out rate while on therapy more often (24% vs 5.3%) than that of carboplatin. Toxicities from chemotherapy were moderate but manageable.