A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer.

OBJECTIVE: To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer. METHODS: Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m(2) and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete+partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP). RESULTS: Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6%) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed. CONCLUSION: Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.

A phase II trial of thalidomide in patients with refractory uterine carcinosarcoma and correlation with biomarkers of angiogenesis: a Gynecologic Oncology Group study.

OBJECTIVES: To evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome. METHODS: Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS)≥6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes. RESULTS: Of 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1-13%) experienced a partial response, and 8 (18%; 90% CI 9-30%) had PFS≥6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2-3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival. CONCLUSIONS: Treatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.

Familial trends in a population with macular holes.

PURPOSE: To determine if patients with macular hole report an increased family history of macular hole compared with control patients and compare the report of family history between patients with unilateral and bilateral macular holes. METHODS: This was a multicenter case-control study. Charts of patients coded with diagnosis of macular hole were reviewed, and the diagnosis of idiopathic full-thickness macular hole was ascertained in 166 patients. The control group comprised 136 patients without macular hole or trauma who presented with senile cataract. Family history was obtained from all patients through a telephone interview. RESULTS: Six of 166 (3.6%) macular hole patients surveyed reported a history of macular hole in a primary relative compared with none of 136 (0.0%) control patients (odds ratio is infinity, with 95% confidence interval 1.295 to infinity); however, this finding may be explained by confounders such as age and number of family members. Two of the 142 (1.4%) patients with unilateral holes versus 4 of the 24 (16.7%) patients with bilateral holes reported a family history (odds ratio is 0.0714, with 95% confidence interval 0.0063 to 0.5537), and this finding remains significant when logistic regression is performed to evaluate variables of age and number of family members as potential confounders. CONCLUSION: There is an increased report of familial occurrence of macular hole in patients with macular holes compared with control patients; however, logistic regression relates this finding to variables of age and number of family members. Patients with bilateral macular holes are more likely to report a family history of macular hole than patients with unilateral macular holes, and this finding remains significant in the presence of age and number of family members. These findings may suggest a familial component to macular hole.

A phase II evaluation of mifepristone in the treatment of recurrent or persistent epithelial ovarian, fallopian or primary peritoneal cancer: a gynecologic oncology group study.

OBJECTIVE: To evaluate the effectiveness and toxicity of mifepristone in patients with ovarian, peritoneal and fallopian tube cancers. METHODS: Patients with confirmed epithelial ovarian, peritoneal and fallopian tube cancers which were persistent or recurred in less then 1 year after primary chemotherapy were entered into this study. Patients were given mifepristone 200 mg by mouth daily for a 28 day cycle. The medication was stopped for unacceptable toxicity or tumor progression. RESULTS: Twenty-four patients were entered into the study. Twenty-two patients were evaluable for response. Only one patient had a partial response for a response rate of only 4.5% (90% confidence interval: 0.2%, 19.8%). CONCLUSION: Mifepristone has not proven to be an effective agent in the treatment of patients with recurrent or persistent ovarian, peritoneal and fallopian tube cancers.

Adenocarcinoma of the cervix metastatic from a colon primary and diagnosed from a routine pap smear in a 17-year-old woman: a case report.

BACKGROUND: Carcinoma metastatic to the uterine cervix is very rare. The most frequent nongenital primary sites are the stomach and colon. CASE: A 17-year-old woman presented to the office for an annual gynecologic examination. The Pap smear and cervical biopsy of a 1.5-cm lesion were positive for adenocarcinoma. Subsequent surgery revealed a sigmoid tumor with extensive abdominal and pelvic carcinomatosis. Following 2 cycles of ineffective chemotherapy, the patient died 4 months after her initial visit to the gynecologist. CONCLUSION: To our knowledge, this was the youngest patient in the literature with colon cancer metastatic to the cervix. This case focuses attention on the diagnostic challenge posed by an incidental finding of a cervical adenocarcinoma in the presence of an asymptomatic primary tumor.

Completion of adjuvant chemotherapy and use of health services for older women with epithelial ovarian cancer.

PURPOSE: This analysis identifies factors associated with completion of adjuvant chemotherapy for patients with ovarian cancer and subsequent use of health services. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare database to identify 4,617 women age 65 years or older with ovarian cancer diagnosed from 2001 to 2005. By using multivariable analyses with completion of chemotherapy as the outcome of interest, we describe factors associated with completion of treatment, including age, race, marital status, comorbidities, and sociodemographic factors. Use of health services was captured from Medicare claims. RESULTS: Among 4,617 patients with untreated ovarian cancer, 1,329 (28.8%) received no chemotherapy, 1,139 (24.7%) received a partial course of chemotherapy, and 2,149 (46.5%) completed chemotherapy. Women age 75 years or older were at greater risk of incomplete chemotherapy versus women age 65 to 74 years (odds ratio [OR], 1.64; 95% CI, 1.33 to 2.04). Having two or more comorbidities was also significantly associated with incomplete chemotherapy (OR, 1.83; 95% CI, 1.34 to 2.50). Among women who received either a partial or complete course of chemotherapy, we did not find an increase in use of health services (hospitalizations, emergency department visits, or physician visits) for the oldest women (age 80 years or older) compared with younger women. CONCLUSION: There is considerable room for improvement in helping older patients with ovarian cancer initiate and complete chemotherapy. The oldest women who completed chemotherapy in this study did not use health services more than younger women did. Treatment teams for older patients with ovarian cancer should include expertise in geriatric assessment, should carefully identify medical and psychosocial barriers to completing treatment, and should support patients throughout treatment.

Regional variation in cancer-directed surgery and mortality among women with epithelial ovarian cancer in the Medicare population.

BACKGROUND: Regional differences in health services can point to disparities in access to healthcare. The authors performed a population-based cohort study to examine differences in ovarian cancer treatment and mortality according to geographic region. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify 4589 women aged ≥65 years with ovarian cancer diagnosed between 1998 and 2002 who had Medicare claims filed from 1998 to 2005. Hospital Referral Region (HRR) was assigned according to patient zip code. The authors calculated the proportion of women in each HRR who underwent cancer-directed surgery. With HRR as the predictor of interest, mortality and the receipt of cancer-directed surgery were described in multivariate analyses. RESULTS: Among 4589 women with ovarian cancer, 3286 underwent cancer-directed surgery. The receipt of cancer-directed surgery varied by HRR (range, 53%-88%). Women were less likely to undergo cancer-directed surgery if they were older, nonwhite, had higher stage disease, or had more comorbidities. For example, white women were more likely to undergo such surgery (odds ratio, 1.41; 95% confidence interval, 1.10-1.82) compared with all nonwhite women. HRR was a significant predictor of cancer-directed surgery (P = .01). A significant correlation was observed between HRR and all-cause mortality (P = .02); however, after adjusting for cancer-directed surgery, that correlation was no longer significant (P = .10). CONCLUSIONS: There was regional variation in mortality among Medicare recipients with ovarian cancer, and access to cancer-directed surgery explained some of that variation. Improving access to high-quality cancer surgery for ovarian cancer may improve outcomes, particularly for minorities and for older women.