Edward C. Grendys

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.

Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study.

Few data are available to help predict which older cancer patient is at risk of developing chemotherapy-related toxicity. This study was a pilot for a project designing a predictive risk score. Chemotherapy patients aged 70 years and older were prospectively enrolled. Chemotherapies were adjusted for their published toxicity. 60 patients were enrolled, 59 were evaluable. Mean dose-intensity was 90.3%, range 33.3-129.0%. 47% of the patients experienced grade 4 haematological and/or grade 3-4 non-haematological toxicity. Published toxicity (MAX2), diastolic blood pressure, marrow invasion and lactate dehydrogenase (LDH) were all associated with toxicity (P<0.1); Body Mass Index, previous chemotherapy, red blood cells, platelets, polymedication with dose-intensity; and polymedication with FACT-G change. After adjustment for the published toxicity, the variables retained their significance, except for LDH and polymedication (for dose-intensity). Although the size of this pilot study imposes a cautious interpretation, patient-related and chemotherapy-related variables correlated independently with toxicity. Designing a composite predictive score to use in assessing the toxicity of multiple chemotherapy regimens therefore appears to be a valid undertaking.

Ovarian cancer in pregnancy.

A pelvic mass in pregnancy is a relatively common entity, especially considering the increased use of ultrasound or early fetal evaluation. These masses can derive from multiple gynecologic and nongynecologic origin, and fortunately the majority will resolve with observation into the second trimester. Masses persisting into the second trimester should be surgically evaluated given the decreased risk to both mother and fetus at this time. For masses persisting into the third trimester, a 2% to 5% risk of malignancy is to be expected. Documentation of disease (FIGO stage) is critically important in defining need for adjuvant cytotoxic chemotherapy. Above all, potentially lifesaving therapy should not be withheld from patients because they are pregnant, especially considering that chemotherapy is apparently safe in the second and third trimesters.

Reproductive technologies and risk of ovarian cancer.

Use of artificial technologies is increasing within the United States. Unfortunately, data describing the possible effects of ‘superovulation’ and potential risk of subsequent ovarian carcinoma are not well defined. This discussion focuses on current data regarding the potential for increased risk for ovarian carcinoma in patients who have undergone infertility evaluation and subsequent treatments.

Disparities in treatment and survival for women with endometrial cancer: A contemporary national cancer database registry analysis

PURPOSE The study aim was to identify contemporary socioeconomic, racial, ethnic, and facility-related factors associated with stage at diagnosis, receipt of cancer treatment, and survival in women with endometrial cancer (EC). PATIENTS AND METHODS Women diagnosed with EC between 1998 and 2010 were identified from the National Cancer Database. Variables associated with the outcomes of interest were assessed using multivariable Cox proportional hazards and logistic regression. RESULTS Among 228,511 women identified, the percentage of blacks with stage IIIC/IV disease at diagnosis was nearly twice that of non-Hispanic whites (17.8% vs 9.8%; P<0.001). Patients with advanced disease who were insured with Medicare were less likely to receive standard-of-care postoperative radiotherapy and/or chemotherapy than those with private insurance (odds ratio: OR 0.80, P<0.001), as were those residing in the South (reference) in comparison to the Northeast, Atlantic, Great Lakes, and Midwest regions (OR 1.3-1.7, all P<0.001). Those residing in the Mountain region were even less likely to receive appropriate treatment (OR 0.7, P<0.001). Five-year stage IIIC/IV survival was 42.8% for non-Hispanic whites vs 24.6% for blacks (hazard ratio 1.3, P<0.001). Other factors associated with inferior 5-year survival included payer status (not insured, Medicaid, Medicare, vs private, ORs 1.2-1.3, all P<0.01), and treatment at low-volume centers (<5 vs ≥30cases/year, HR 1.3, P<0.001). CONCLUSIONS AND RELEVANCE Socioeconomic, geographic and facility-related factors predict advanced endometrial cancer stage, failure to receive cancer care, and shorter survival. Black women had especially poor survival. Nationwide standardization and concentration of treatment at high-volume centers may improve outcomes.

Infectious urinary tract morbidity with prolonged bladder catheterization after radical hysterectomy

OBJECTIVE This study was undertaken to determine the incidence of catheter-associated infection after radical hysterectomy and to evaluate the role of prophylactic antibiotics in these patients. STUDY DESIGN A 4-year retrospective review of 102 women undergoing radical hysterectomy for cervical or endometrial cancer was performed. Clinical data were abstracted and analyzed with chi(2) and t tests. RESULTS Catheter-associated infection was observed in 11% (12 of 102) and was not altered by the administration of prophylactic antibiotics (11.1% vs 11.8%, P=.95). Of the 12 women who had infection, 11 were treated as outpatients, and 1 patient required admission for pyelonephritis. Patient age, comorbid medical conditions, class of radical hysterectomy, perioperative complications, operative time, blood loss, catheter type, duration of catheterization, and length of hospitalization had no effect on the development of catheter-associated infection. CONCLUSION The incidence of catheter-associated infection in women requiring prolonged catheterization after radical hysterectomy is relatively low. Withholding prophylactic antibiotics from these patients is a reasonable clinical option.

Innovations in the management of vulvar carcinoma.

Radical surgery has resulted in impressive cure rates in women with locally advanced vulvar carcinoma. Unfortunately, morbidity mostly related to inguinofemoral lymphadenectomy, is common. The present review discusses innovations in the management of vulvar disease with attempts to reduce attendant morbidity.

Tolerability, Efficacy, and Safety of Pegylated Liposomal Doxorubicin in Combination with Carboplatin Versus Gemcitabine–Carboplatin for the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review

OBJECTIVE To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature. METHODS Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem-Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies. RESULTS Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem-Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD-Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem-Carbo populations, respectively. The median OS was longer for the PLD-Carbo regimen (27.1 months) than for the Gem-Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem-Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem-Carbo, 62.9%) were more common in patients receiving Gem-Carbo. CONCLUSION Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem-Carbo for the treatment of patients with PSROC.

Preservation of multiple oncogenic human papillomavirus types in recurrences of early-stage cervical cancers

OBJECTIVES Our purpose was to determine the relationship between human papillomavirus genotypes contained in primary early stage cervical cancers and those contained in the respective recurrences. STUDY DESIGN Six early-stage cervical cancers that were considered cured by surgical extirpation subsequently recurred within 21 months of the original surgery. The primary tumors and the recurrences underwent polymerase chain reaction for human papillomavirus typing with confirmation of types performed by means of diagnostic restriction fragments. RESULTS All primary tumors and recurrences contained human papillomavirus, with all primary tumors positive for multiple types. The concordance rate between the primary tumors and recurrences for specific types was 73% (11/15). Among the highly oncogenic types 16 and 18 there was 100% concordance between primary and recurrent tumors. CONCLUSIONS Highly oncogenic types of human papillomavirus are preserved between primary tumors and their recurrences in cervical cancers. This further supports the role of oncogenic types in the maintenance of the malignant state and supports the clonogenic nature of cervical cancer recurrence.

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things

OBJECTIVE Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.