Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer.

OBJECTIVE: To determine the ability of patients to be treated with biweekly bevacizumab and weekly taxane chemotherapy in women with advanced, refractory ovarian cancer. METHODS: Ten patients with advanced, recurrent, and refractory ovarian cancer who were treated with biweekly bevacizumab (10 mg/kg) and weekly taxane (paclitaxel or docetaxel) chemotherapy days 1, 8, 15, and 22 every 28 days were identified retrospectively. All patients were followed with serial CA125 measurements prior to each cycle of therapy; cross-sectional imaging was not used to follow response to therapy. Toxicities were assessed prior to each cycle of treatment. RESULTS: Of the 10 patients treated with weekly taxane and biweekly bevacizumab therapy, all 9 that were evaluable had a decrease in CA125. Five patients have had an increase in CA125 after therapy after a median of three cycles (range 1-4), while 3 patients experienced normalization of CA125 and another with continued improvement in CA125. All symptomatic patients experienced rapid palliation of pain, nausea, and ascites. Side effects have been mild, with no grade 3 or 4 toxicities noted. No treatment delays or discontinuations have been necessary. CONCLUSION: Treatment of advanced, recurrent, refractory epithelial ovarian cancer with bevacizumab and weekly taxane chemotherapy leads to significant, albeit temporary, improvement in the cancer-related symptoms in women treated on this regimen, and short-term exposure to these agents is not associated with significant toxicity. Thus, continued investigation of bevacizumab with weekly scheduling of cytotoxic chemotherapy is imperative.

Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study.

OBJECTIVES: The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. METHODS: Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1-3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), Neurotoxicity Subscale (FACT/GOG-NTX subscale), and Brief Pain Inventory (BPI). RESULTS: One hundred eighty-six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. CONCLUSIONS: MVAC's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.

Case report: malignant peritoneal mesothelioma in two siblings.

BACKGROUND: Mesothelioma is a rare tumor, linked with occupational asbestos exposure. This association has been used to explain clustering of cases within families. Newer evidence, however, supports a possible genetic predisposition for this tumor. CASE: Our patient's brother was diagnosed with advanced stage malignant peritoneal mesothelioma in August 1995 at age of 42, he underwent tumor-reductive surgery followed by chemotherapy. He underwent a repeat cytoreductive surgery in September 1996 and further chemotherapy. He died of disease in December 1996. Our patient underwent cytoreductive surgery in May 1999 at age of 49 for advanced stage malignant peritoneal mesothelioma with suboptimal debulking. She received multiple chemotherapy regimens, including most recently experimental targeted agents, for slow progressing disease. She is presently alive with clinical disease 6 years from diagnosis. CONCLUSION: This is the first report of two siblings of different gender with malignant peritoneal mesothelioma and only average environmental asbestos exposure. It is highly likely that the family described in this case report has some form of inherited susceptibility to malignancy cancer gene, HLA type, or tumor suppressor gene mutation.

Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

PURPOSE: On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive cisplatin 50 mg/m(2) every 3 weeks (CPT); cisplatin 50 mg/m(2) day 1 plus topotecan 0.75 mg/m(2) days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m(2) days 1, 15, and 22, vinblastine 3 mg/m(2) days 2, 15, and 22, doxorubicin 30 mg/m(2) day 2, and cisplatin 70 mg/m(2) day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. RESULTS: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. CONCLUSION: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Morbid obesity and endometrial cancer: surgical, clinical, and pathologic outcomes in surgically managed patients.

OBJECTIVE: To evaluate surgical, clinical, and pathologic outcomes of patients with endometrial cancer managed with primary surgery when stratified by body mass index (BMI). METHODS: A review of 356 consecutive patients undergoing primary surgical management of endometrial carcinoma by a single gynecologic oncology service from 1997 to 2003 was undertaken. Patients were divided into three groups based on preoperative BMI. Data regarding surgical and pathologic outcomes were compared. RESULTS: Twenty-two percent of patients had a BMI >40, 38% were 30-40, and 40% were <30. Overall, 90% underwent some surgical staging, including 93%, 92%, and 81% of those with a BMI <30, 30-40, and >40, respectively. In fully staged patients, a median 23 lymph nodes were removed in all groups, without a significant difference in the number of aortic nodes recovered between the heaviest and lightest groups. Aortic lymphadenectomy was performed in 48% patients with BMI >40 compared with 74% of patients with BMI <30. Intraoperative and postoperative complications were rare and similar between groups. Patients with BMI >40 were more commonly diagnosed with grade 1 tumor than patients with BMI <30. Rates of nodal metastasis were similar between groups and occurred in 11% of patients overall. In those with a BMI >40, extrauterine disease was encountered in 12% of patients. CONCLUSIONS: While surgical staging of morbidly obese patients is difficult, adequate lymphadenectomy can be performed safely; although aortic nodes are less commonly resected in this population. Staging remains important in obese women, as the risk of extrauterine disease, including lymph node metastasis, is similar to that in women with ideal body weight.

Is there a prognostic difference between depth of myometrial invasion and the tumor-free distance from the uterine serosa in endometrial cancer?

OBJECTIVE: The objective was to determine whether tumor-free distance from the uterine serosa is more predictive of patient outcome than depth of endometrial cancer invasion into the myometrium. METHODS: Patients with surgically staged endometrial adenocarcinoma between 1997 and 2000 were identified. Depth of myometrial invasion (DOI) was identified defined as the distance between endometrial-myometrial junction and deepest myometrial invasion. Tumor-free distance from the uterine serosa (TFD) was defined as the distance between the serosa and deepest myometrial invasion. DOI and TFD were expressed as continuous variables and compared with traditional surgicopathologic variables, recurrence, and survival to determine their predictive and prognostic significance. RESULTS: We identified 153 patients who met study criteria. The median DOI was 0.5 cm and the median TFD was 1.4 cm. The most common stage was IB, and 23 patients had positive nodes. With a median follow-up of 29 months, 10 patients have recurred. When DOI and TFD were compared in a univariate model, TFD was an equal or more significant predictor of traditional surgicopathologic variables. TFD but not DOI was predictive of recurrence. Likewise, TFD was a more significant predictor of dying from disease than DOI. In a multivariate model, TFD was shown to correlate with surgicopathologic variables, recurrence risk, and survival. DOI, however, was not predictive unless myometrial thickness was included in the model. A TFD of 1 cm maximized the balance of sensitivity and specificity in predicting recurrence. CONCLUSION: TFD as a single measurement carries significant prognostic importance in women with comprehensively staged endometrial cancer.

Pre-emptive analgesia in gynecologic surgical procedures: preoperative wound infiltration with ropivacaine in patients who undergo laparotomy through a midline vertical incision.

OBJECTIVE: We tested the hypothesis that local anesthetic that is injected before a vertical midline abdominal incision would decrease the use of postoperative opioids. STUDY DESIGN: Patients who would undergo abdominal surgical procedures with general anesthesia by a planned vertical midline incision were enrolled in the study. Patients were assigned randomly to receive either 0.5% ropivacaine or normal saline solution placebo that was injected in the subcuticular tissue and fascia before the incision of each. All patients received morphine after the operation with a patient-controlled analgesia device. Morphine consumption was measured during the postoperative period at intervals of 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, and 24 to 48 hours. Postoperative pain was assessed at 6, 12, 24, and 48 hours after the conclusion of the procedure with a visual analog scale. RESULTS: Eighty-four patients were enrolled in the study; 16 patients were excluded; therefore, 68 patients had useable data. The two treatment groups did not differ in age, height, weight, the length of the operation, the length of the incision, the position of the incision, the placement of drains, or the procedure that was performed. There was no significant difference in morphine consumption for any of the four intervals. The visual analog scale was not significantly different between the two groups at 6, 12, or 24 hours after operation. The visual analog scale at 48 hours was lower in the group that received ropivacaine (2.69 vs 4.26, P =.02). Data were analyzed by the Student t test. CONCLUSION: Pre-emptive analgesia with 0.5% ropivacaine given before skin incision does not decrease the postoperative analgesic use in patients who undergo laparotomy by a midline vertical skin incision.

Ureteroileoneocystostomy: the use of an ileal segment for ureteral substitution in gynecologic oncology.

OBJECTIVE: The aim of this study was to assess the results of the use of an ileal segment to restore the functional integrity of the renal tract where lower ureteric resection is necessary in gynecologic oncology surgery. METHODS: All patients in whom ureteroileoneocystostomy (UINC) was performed between March 1988 and December 2000 were identified and a retrospective review of their case notes was conducted. RESULTS: A total of 12 UINC procedures were performed on eight patients. The primary diagnoses were ovarian cancer in six cases, endometrial stromal sarcoma in one case, and vaginal carcinoma in one case. The average age of the patients at the time of their first UINC procedure was 56 years. Bilateral UINC was performed at a single episode in one patient and unilateral UINC in seven patients. Subsequent obstruction necessitated repeat or revision of the original procedure in two cases and contralateral UINC in one case. Complications included one death at 38 days from aspiration pneumonia not directly related to UINC, one pelvic abscess causing ureteric obstruction, and three cases of recurrent urinary tract infection. Follow-up ranged from 38 days to 77 months following the initial UINC procedure, with a mean of 34 months. Aside from the single postoperative death, the procedure was successful in 82% (9/11) of anastamoses on the first occasion and 100% (2/2) of anastamoses at repeat or revision surgery. There were no cases of renal failure secondary to a failed UINC. CONCLUSIONS: Ureteroileoneocystostomy is a safe and effective procedure that should be considered in cases where lower ureteric resection is necessary.