Incidence and predictors of toxicity in the management of vulvar squamous cell carcinoma treated with radiation therapy.

Purpose/Objective: Given the rarity of vulvar cancer, data on the incidence of acute and late severe toxicity and patients' symptom burden from radiotherapy (RT) are lacking. Materials/Methods: This multi-center, single-institution study included patients with vulvar squamous cell carcinoma treated with curative intent RT between 2009 and 2020. Treatment-related acute and late grade ≥ 3 toxicities and late patient subjective symptoms (PSS) were recorded. Results: Forty-two patients with predominantly stage III/IV disease (n = 25, 59.5 %) were treated with either definitive (n = 25, 59.5 %) or adjuvant (n = 17, 40.5 %) external beam RT to a median dose of 64 Gy and 59.4 Gy, respectively. Five patients received a brachytherapy boost with a median total dose of 84.3 Gy in 2 Gy-equivalent dose (EQD2). Intensity-modulated RT was used in 37 (88.1 %) of patients, and 25 patients (59.5 %) received concurrent chemotherapy. Median follow-up was 27 months. Acute grade ≥ 3 toxicity occurred in 17 patients (40.5 %), including 13 (31.0 %) acute grade 3 skin events. No factors, including total RT dose (p = 0.951), were associated with acute skin toxicity. Eleven (27.5 %) patients developed late grade ≥ 3 toxicity events, including 10 (23.8 %) late grade ≥ 3 skin toxicity events. Patients with late grade ≥ 3 skin toxicity had a higher mean body-mass index (33.0 vs 28.2 kg/m2; p = 0.009). Common late PSS included vaginal pain (n = 15, 35.7 %), skin fibrosis (n = 10, 23.8 %), and requirement of long-term opiates (n = 12, 28.6 %). Conclusion: RT for vulvar cancer is associated with considerable rates of severe acute and late toxicity and PSS burden. Larger studies are needed to identify risk factors, explore toxicity mitigation strategies, and assess patient-reported outcomes.

Thirty-day Postoperative Adverse Events in Minimally Invasive versus Open Abdominal Radical Hysterectomy for Early-stage Cervical Cancer.

STUDY OBJECTIVE: To identify the incidence, type, and grade of postoperative adverse events in minimally invasive radical hysterectomy vs abdominal radical hysterectomy (ARH) for patients with early-stage cervical cancer and determine risk factors associated with these adverse events. DESIGN: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was queried to identify patients with early-stage cervical cancer undergoing radical hysterectomy. Multivariable logistic regression was used to assess risk factors associated with adverse postoperative outcomes among patients undergoing radical hysterectomy. SETTING: ACS NSQIP participating institutions within the United States. PATIENTS: Patients were collected from the ACS NSQIP databases (2014-2017) undergoing radical hysterectomy for early-stage cervical cancer. INTERVENTIONS: N/A MEASUREMENTS AND MAIN RESULTS: ARH had a significantly increased incidence of any 30-day postoperative adverse event compared with minimally invasive radical hysterectomy (31.2% vs 19.9%, p <.001). There was a higher incidence of surgical site infection, both deep and superficial, and blood transfusions in ARH. On multivariable logistic regression, the abdominal surgical approach was the only risk factor significantly associated with any postoperative adverse event (odds ratio, 1.4; confidence interval, 1.1-1.9; p = .018; 95% CIs). CONCLUSIONS: In this study, the abdominal surgical approach for radical hysterectomy in early-stage cervical cancer was associated with a higher incidence of postoperative adverse events than the minimally invasive approach.

What Should a Gynecologist Know about Li-Fraumeni Syndrome? Lessons from a Patient Undergoing Hysterectomy for Benign Indications.

Li-Fraumeni syndrome (LFS) is a rare highly penetrant cancer syndrome characterized by mutation in the TP53 tumor suppressor gene. Recent data suggest that this germline mutation is more frequent than once thought. While LFS has not been associated previously with pelvic serous carcinoma, gynecologic malignancies have been reported in this patient population. We present the case report of a 37-year-old patient with known LFS and a history of multiple cancers who underwent total abdominal hysterectomy for benign indications with incidental bilateral salpingo-oophorectomy. On final pathology, she was found to have serous tubal intraepithelial carcinoma of bilateral fallopian tubes. Our findings raise the question of the potential role of prophylactic gynecologic cancer-reducing surgery in this patient population.

Outcomes and Cost Analysis of Surveillance Strategies After Initial Treatment for Women With Recurrent Ovarian Cancer.

OBJECTIVE: The aim of this study was to determine whether there is a survival or cost benefit dependent on detection strategy of recurrent ovarian cancer (ie, imaging, physical examination findings, report of symptoms, or rising cancer antigen 125 [CA-125] levels). METHODS/MATERIALS: A retrospective chart review of 112 ovarian cancer patients was conducted, and method of detection of recurrent disease was determined from medical records. The following primary outcomes were determined using Cox proportional hazards regression model: progression-free survival (PFS) after diagnosis of recurrence and time to death after diagnosis of recurrence (overall survival [OS]). Several approaches to disease surveillance were proposed, and a cost model was applied. RESULTS: Median time to recurrence was 13.5 months. Overall, 6.3% presented with only physical examination findings; 24.1%, with elevating CA-125 levels; 34.8%, with imaging; and 32.1%, with symptoms. Most patients presenting with recurrent disease diagnosed by rising CA-125 were white (62.9%); those with imaging and symptomatic recurrences were blacks (56.4% and 57.1%, respectively). There was a small but not statistically significant OS benefit for recurrence detected via CA-125 (P = 0.85; OS per detection method: PE, 20.7 months; CA-125, 26.8 months; imaging, 17.8 months; and symptoms, 6.6 months). We modeled costs of surveillance in our patient cohort; up to 40.8% of cases of ovarian cancer recurrences would have been missed if no imaging were obtained during surveillance. CONCLUSIONS: Results indicate minimal differences in PFS and statistically insignificant differences in OS, depending on detection method. Notably, black patients with Medicaid presented most often with symptomatic recurrences, which surprisingly did not affect patient OS and PFS; and interestingly, pr\ivate or self-pay insurance was associated with decreased OS among black patients. From our cost analysis, we estimate that the most cost-effective surveillance strategy for the first year costs $9.2 million annually and includes office visit biannually, biannual CA-125 levels, and annual asymptomatic imaging.

Ovarian carcinoma initially presenting as breast cancer two years prior to diagnosis: A case report and review of literature.

•Ovarian cancer presenting as a primary breast cancer two years prior•Ovarian cancer with metastases to breast is rare.•Metastases to the breast generally present as a recurrence.•Delay in diagnosis likely due to chemotherapy given for breast disease.

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.

OBJECTIVE: To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. METHODS: In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m(2) (cohorts A1 and A3, respectively) or topotecan 4 mg/m(2) (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary). RESULTS: 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent. CONCLUSIONS: Trebananib 10mg/kg and 15 mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.

Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer.

OBJECTIVE: The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC). METHODS: Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1,000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for ≤ 12 months. Patients without CR received single-agent crossover therapy at induction doses/schedules until CR, disease progression (PD), or unacceptable toxicity. PD or death in 636 patients was required to compare induction arms with 80% statistical power for progression-free survival (PFS), the primary endpoint. RESULTS: Randomized induction therapy was received by 820 of 919 patients enrolled; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy. PFS was similar for GC and TC (median, 20.0 and 22.2 months, respectively; P=.199). Despite high censoring rates (>52%), overall survival was longer for TC (median, 57.3 versus 43.8 months for GC; P=.013). Controlling for patient characteristics including performance status, residual tumor size, and tumor stage, there was no statistical difference in a multivariate analysis (HR=1.22; 95% CI=0.99-1.52; P=.067). CONCLUSIONS: GC does not improve PFS over TC as first-line induction chemotherapy in OC. Although favoring TC, overall survival analyses were limited by the study design and high censoring rates.

Overexpression of tumor vascular endothelial growth factor A may portend an increased likelihood of progression in a phase II trial of bevacizumab and erlotinib in resistant ovarian cancer.

PURPOSE: This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer; exploratory biomarker analyses, including that of tumor vascular endothelial growth factor A (VEGF-A), were also done. EXPERIMENTAL DESIGN: Forty heavily pretreated patients received erlotinib (150 mg/d orally) and bevacizumab (10 mg/kg i.v.) every 2 weeks until disease progression. Primary end points were objective response rate and response duration; secondary end points included progression-free survival (PFS), toxicity, and correlations between angiogenic protein levels, toxicity, and efficacy. RESULTS: Grade 3 toxicities included skin rash (n = 6), diarrhea (n = 5), fatigue (n = 4), and hypertension (n = 3). Grade 4 toxicities were myocardial infarction (n = 1) and nasal septal perforation (n = 1). Only one grade 3 fistula and one grade 2 bowel perforation were observed. Nine (23.1%) of 39 evaluable patients had a response (median duration, 36.1+ weeks; one complete response), and 10 (25.6%) patients achieved stable disease, for a disease control rate of 49%. Median PFS was 4 months, and 6-month PFS was 30.8%. Biomarker analyses identified an association between tumor cell VEGF-A expression and progression (P = 0.03); for every 100-unit increase in the VEGF-A score, there was a 3.7-fold increase in the odds of progression (95% confidence interval, 1.1-16.6). CONCLUSIONS: Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinically active and well tolerated. Erlotinib did not seem to contribute to efficacy. Our study raises the intriguing possibility that high levels of tumor cell VEGF-A, capable of both autocrine and paracrine interactions, are associated with resistance to bevacizumab, emphasizing the complexity of the tumor microenvironment.

Pegfilgrastim on the Same Day Versus Next Day of Chemotherapy in Patients With Breast Cancer, Non-Small-Cell Lung Cancer, Ovarian Cancer, and Non-Hodgkin's Lymphoma: Results of Four Multicenter, Double-Blind, Randomized Phase II Studies.

PURPOSE: To compare data on severe (grade 4) neutropenia duration and febrile neutropenia incidence in patients receiving chemotherapy with pegfilgrastim administered the same day or 24 hours after chemotherapy. PATIENTS AND METHODS: These were similar, randomized, double-blind phase II noninferiority studies of patients with lymphoma or non-small-cell lung (NSCLC), breast, or ovarian cancer. Each study was analyzed separately. The primary end point in each study was cycle-1 severe neutropenia duration. Approximately 90 patients per study were to be randomly assigned at a ratio of 1:1 to receive pegfilgrastim 6 mg once per cycle on the day of chemotherapy or the day after (with placebo on the alternate day). RESULTS: In four studies, 272 patients received chemotherapy and one or more doses of pegfilgrastim (133 same day, 139 next day). Three studies (breast, lymphoma, NSCLC) enrolled an adequate number of patients for analysis. However, in the NSCLC study, the neutropenic rate was lower than expected (only two patients per arm experienced grade 4 neutropenia). In the breast cancer study, the mean cycle-1 severe neutropenia duration was 1.2 days (95% confidence limit [CL], 0.7 to 1.6) longer in the same-day compared with the next-day group (mean, 2.6 v 1.4 days). In the lymphoma study, the mean cycle-1 severe neutropenia duration was 0.9 days (95% CL, 0.3 to 1.4) longer in the same-day compared with the next-day group (mean, 2.1 v 1.2 days). In the breast and lymphoma studies, the absolute neutrophil count profile for same-day patients was earlier, deeper, and longer compared with that for next-day patients, although the results indicate that same-day administration was statistically noninferior to next-day administration according to neutropenia duration. CONCLUSION: For patients receiving pegfilgrastim with chemotherapy, pegfilgrastim administered 24 hours after chemotherapy completion is recommended.

Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer.

PURPOSE: To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar (PSC 833) in untreated patients with advanced ovarian or primary peritoneal cancer. PATIENTS AND METHODS: Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were randomly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses, paclitaxel 80 mg/m(2), and carboplatin area under the curve (AUC) 6 (PC-PSC; n = 381) or paclitaxel 175 mg/m(2) and carboplatin AUC 6 (PC; n = 381). Time to disease progression (TTP) was the primary end point. Secondary end points were overall survival time (OS), response rate (RR), safety, and tolerability. RESULTS: With a median follow-up of 736 days (range, 1 to 2,280 days), the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups, respectively (P = .67); the median OS was 32 and 28.9 months, respectively (P = .94). The overall RR was higher in the PC group (41.5% v 33.6%; P = .02). Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group. Ataxia occurred in 53.5% and 3.2% of PC-PSC-and PC-treated patients, respectively. Febrile neutropenia occurred more frequently in the PC-PSC group. More PC-PSC-treated patients discontinued therapy because of adverse events (AEs), experienced serious AEs, and required paclitaxel dose reductions. CONCLUSION: The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer.

Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer.

PURPOSE: Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. PATIENTS AND METHODS: Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. RESULTS: In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. CONCLUSION: Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer.

OBJECTIVE: To determine the safety and efficacy of a novel illudin S derivative, irofulven (MGI-114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. METHODS: The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/m2. Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non-hematologic toxicities. RESULTS: Seventy-four women were accrued and stratified into two cohorts including 58 women with platinum-resistant disease and 16 with platinum-sensitive disease. Non-hematologic toxicities included nausea, vomiting, and fatigue. Thirty-one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post-treatment with irofulven. There was one partial response in each cohort with 19 (33%) and 8 (50%) of women having stable disease in the platinum-resistant and platinum-sensitive cohorts, respectively. CONCLUSIONS: Irofulven at 24 mg/m2 on every 14-day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti-tumor activity in a population of women who had received extensive prior chemotherapy.

Validation of referral guidelines for women with pelvic masses.

OBJECTIVE: Guidelines for referring women with pelvic masses suspicious for ovarian cancers to gynecologic oncologists have been published jointly by Society of Gynecologic Oncologists (SGO) and the American College of Obstetricians and Gynecologists (ACOG). They are based on patient age, CA 125 level, physical findings, imaging study results, and family history. Although the guidelines are evidence-based, their predictive value in distinguishing cancers from benign masses is unknown. METHODS: Chart review for factors included in the guidelines of surgically evaluated women with pelvic masses at 7 tertiary care centers during a 12-month interval was performed. This information was used to estimate the predictive values of the SGO and ACOG guidelines in identifying patients with malignant pelvic masses. RESULTS: A total of 1,035 patients were identified, including 318 (30.7%) with primary malignancies of the ovary, fallopian tube, or peritoneum. Seventy-seven were younger than 50 years old (premenopausal group), and 240 were 50 years old or older (postmenopausal group). Fifty additional patients (4.8%) had cancers metastatic to the ovaries, and the remaining 667 (64.4%) had benign masses. The referral guidelines captured 70% of the ovarian cancers in the premenopausal group and 94% of the ovarian cancers in the postmenopausal group. The positive predictive value was 33.8% for the premenopausal group and 59.5% for the postmenopausal group, whereas the negative predictive values were more than 90% for both groups. Elevated CA 125 level was the single best predictor of malignancy in both groups. CONCLUSION: The SGO and ACOG referral guidelines effectively separate women with pelvic masses into 2 risk categories for malignancy. This distinction permits a rational approach for referring high-risk patients to a gynecologic oncologist for management.

Role of pegylated liposomal doxorubicin in ovarian cancer.

OBJECTIVES: Safe, effective treatments are needed for relapsed ovarian cancer. Goals include improving symptoms, enhancing quality of life, and prolonging survival. The plethora of agents currently available present difficult choices for physicians. The present effort seeks to examine the role of one of these agents, pegylated liposomal doxorubicin. METHODS: A roundtable meeting of experts in the management of ovarian carcinoma was held to build consensus around the present and future role of pegylated liposomal doxorubicin for ovarian cancer and other gynecologic malignancies. RESULTS: Pegylated liposomal doxorubicin is effective and well tolerated in relapsed ovarian cancer. When compared with topotecan in a phase III randomized trial, pegylated liposomal doxorubicin showed several advantages: improved quality of life, fewer severe adverse events, fewer dose modifications, less hematologic support, and lower total cost per patient. In platinum-sensitive patients, pegylated liposomal doxorubicin also produced a survival advantage. Results from prospective and retrospective studies further demonstrate the improved cardiac safety of pegylated liposomal doxorubicin compared to conventional anthracyclines. CONCLUSIONS: Based on survival and toxicity advantages and a once-monthly administration schedule, pegylated liposomal doxorubicin is the first-choice nonplatinum agent for relapsed ovarian cancer. Pegylated liposomal doxorubicin may also have clinical application in combination regimens for platinum-sensitive ovarian cancer, as consolidation/maintenance therapy for ovarian cancer, as a component of first-line therapy for ovarian cancer, and in the treatment of other gynecologic malignancies. Future clinical trials will further define and maximize the role of pegylated liposomal doxorubicin in the treatment of ovarian cancer and other gynecologic malignancies.

Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer.

OBJECTIVE: Provide long-term follow-up data for women treated in a randomized multicenter study of pegylated liposomal doxorubicin compared with topotecan. METHODS: Patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy were randomized to receive pegylated liposomal doxorubicin 50 mg/m(2) every 28 days (n = 239) or topotecan 1.5 mg/m(2) per day for 5 days every 21 days (n = 235). Patients were stratified prospectively based on response to initial platinum-based chemotherapy as well as the presence or absence of bulky disease. Most patients had been previously treated with platinum and taxanes (74% in the pegylated liposomal doxorubicin group and 72% in the topotecan group). Survival data are mature: 87% of patients have died (n = 413). RESULTS: There was an 18% reduction in the risk of death for patients treated with pegylated liposomal doxorubicin (median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients; HR = 1.216; 95% confidence interval (CI) 1.000-1.478; P = 0.050). The hazard ratio for all randomized subjects (includes those randomized, but never treated; n = 481) was 1.23 (median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients; 95% CI 1.01-1.50; P = 0.038). For patients with platinum-sensitive disease, there was a 30% reduction in the risk of death for the pegylated liposomal doxorubicin-treated group (median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients; HR = 1.432; 95% CI 1.066-1.923; P = 0.017). In patients with platinum-refractory disease, survival was similar between treatment groups. CONCLUSION: Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer. The survival benefit is pronounced in patients with platinum-sensitive disease.

CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients.

OBJECTIVE: To evaluate immune responses and clinical outcomes for combined oregovomab and chemotherapy treatment of patients with recurrent ovarian cancer. METHODS: Patients with advanced recurrent ovarian cancer were administered oregovomab over 12 weeks before chemotherapy, then optionally concurrent with chemotherapy x 2. Antibody responses, including human anti-mouse antibody (HAMA), anti-idiotypic antibody (Ab2) and anti-CA125, were assessed by ELISA; T-cell responses to CA125, autologous tumor and oregovomab by interferon (IFN)-gamma enzyme-linked immunoSPOT (ELISPOT) were also evaluated. Clinical outcomes were recorded. RESULTS: Twenty patients were enrolled; median follow-up was 15.8 months. Oregovomab was well tolerated and did not produce drug-related serious adverse reactions. In 15/19 (79%) patients, robust treatment-emergent humoral responses were observed to the constant (HAMA) and variable region (Ab2) of oregovomab, and 2/19 (11%) patients developed anti-CA125 antibodies. Significant increases in T-cell responses were measured in 7/18 (39%) patients in response to CA125, in 5/8 (63%) patients in response to autologous tumor and in 9/18 (50%) patients in response to oregovomab. Immune responses appeared by week 12 (four doses) and were generally maintained or augmented in patients continuing combined treatment with oregovomab and chemotherapy. Median survival was 70.4 weeks (4.6-141.6 weeks), and the median progression-free interval was 11 weeks (2.6-114.6 weeks). Patients who mounted a T-cell response to CA125 and/or autologous tumor showed significantly improved survival (median not reached vs. 51.9 weeks, P = 0.002) compared to patients who did not. CONCLUSIONS: Oregovomab was well tolerated and induced multiple antigen-specific immune responses, maintained during concomitant chemotherapy. A significant survival benefit was observed in patients mounting a T-cell response to CA125 and/or autologous tumor.

Phase II study of sequential doublets: topotecan and carboplatin, followed by paclitaxel and carboplatin, in patients with newly diagnosed advanced ovarian cancer.

OBJECTIVE: Incorporating topotecan into standard platinum/taxane chemotherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclitaxel and carboplatin, in newly diagnosed advanced ovarian cancer patients. METHODS: Forty-five patients (median age, 56 years; range, 38-77 years) with stage III/IV disease and GOG performance status <2 were enrolled and received four cycles of topotecan (1.0 mg/m(2)/day on days 1 to 3) and carboplatin (AUC 4 on day 1), followed by four cycles of paclitaxel (175 mg/m(2) via 3-h IV infusion on day 1) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete response (CR) underwent second-look laparotomy for determination of pathologic CR (PCR). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia, and for grade 3/4 nonhematologic toxicity. RESULTS: Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, respectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progression was 14 months and actuarial survival was 23 months. Neutropenia was the primary toxicity and cause of dose adjustments and delays, including two deaths. CONCLUSION: The antitumor activity observed is comparable with other series, although neutropenic complications were increased. Progression-free and actuarial survivals were slightly inferior. A Phase III trial (GOG 182) of sequential doublets in the reverse sequence is ongoing.

Liposomal anthracycline treatment for ovarian cancer.

Platinum/taxane regimens induce high response rates and prolong survival in women with ovarian cancer. After recurrence, however, response to second-line chemotherapy is limited. Pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), is the only liposomal anthracycline indicated for second-line treatment of platinum- and paclitaxel-refractory ovarian cancer. Response rates ranged from 14% to 20% in nonrandomized trials of this patient population. In a large phase 3 randomized trial, single-agent PLD and topotecan had similar efficacy overall in response rates, but PLD-treated patients had significantly improved overall survival compared with topotecan with a pronounced advantage in platinum-sensitive patients. Another randomized trial reported that PLD and paclitaxel were comparable with regards to response rate, progression-free survival, and overall survival, regardless of the degree of platinum sensitivity. Additional nonrandomized trials of PLD in combination with other active agents resulted in response rates ranging from 20% to 76%. PLD is generally well tolerated and its side-effect profile compares favorably with other commonly used chemotherapeutic agents in this clinical setting. Proper dosing and monitoring may further enhance tolerability while preserving the efficacy of this versatile agent for ovarian cancer.

Chemotherapeutic management of advanced ovarian cancer.

OBJECTIVE: To review current treatment strategies for patients with advanced ovarian cancer. Factors for treatment selection are discussed. DATA SOURCES: Research articles and textbooks. CONCLUSION: Research efforts continue to identify novel agents and/or combination therapies that can effect a cure or prolong survival. Several agents offer similar efficacy outcomes but vary in safety aspects and administration requirements. IMPLICATIONS FOR NURSING PRACTICE: Numerous clinical trials have defined the efficacy and safety of chemotherapy in patients with ovarian cancer. Oncology nurses can prepare patients to make treatment decisions; educate them about treatment-related side effects; and develop an ongoing relationship as patient advocates to ensure quality of life.