Pronounced clinical response following the oncolytic vaccinia virus GL-ONC1 and chemotherapy in a heavily pretreated ovarian cancer patient.

Heavily pretreated ovarian cancer patients become progressively chemoresistant, and thereafter, only scant treatments potentially accord reasonable, albeit limited clinical efficacy. We describe a case involving a 67-year-old ovarian cancer patient who underwent multiple lines of chemotherapy and presented with recurrent disease and a CA-125 of 4112 U/mL. Thenceforth, she was treated with GL-ONC1 oncolytic viral therapy that was administered laparoscopically in accordance with a clinical trial. The patient subsequently received chemotherapy and during the fourth cycle, her CA-125 decreased to 99 U/mL; moreover, a computed tomography scan of the pelvis exhibited significant disease reduction. Viral therapy hypothetically confers significant promise in the treatment of recurrent ovarian cancer, especially in patients who remain unresponsive to traditional medications.

A Prospective, Observational Trial Assessing the Efficacy of Abdominal Compression in Reducing Laparoscopic-Induced Shoulder Pain.

INTRODUCTION: Postoperative shoulder pain is a condition associated with laparoscopic surgery and presumably attributed to residual carbon dioxide (CO2) in the abdomen. The intent of the current prospective, observational study was to assess the efficacy of abdominal compression in mitigating this painful complication. METHODS: We recruited 30 patients who were treated with laparoscopic surgery for the management of gynecologic disease. All study participants underwent abdominal compression to evacuate the CO2 associated with their pneumoperitoneum. Postoperatively, the subjects' pain intensity was measured via the visual analogue scale at 12, 24, and 48 hours. RESULTS: The patients' mean postoperative visual analogue scale pain scores were the highest during the initial 12 hours (1.93), and thereafter, steadily declined at 24 hours (0.73) and 48 hours (0.70) ( P = .045). Furthermore, toxicity was reasonable, with only 20% of subjects who reported grade ≤2 nausea and vomiting. CONCLUSION: Abdominal compression is a relatively safe procedure that appears to sufficently evacuate residual CO2, thereby reducing the severity of laparoscopic surgery induced shoulder pain.

A Randomized Controlled Pilot Study Comparing the Impact of Aprepitant and Fosaprepitant on Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecologic Cancer.

OBJECTIVE: The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting. METHODS AND MATERIALS: Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis. RESULTS: In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy. CONCLUSIONS: The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

The retreatment of carboplatin via high-dose intraperitoneal chemotherapy in patients with a history of a hypersensitivity reaction.

A hypersensitivity reaction attributed to platinum-based chemotherapy is a relatively common occurrence. Hyperthermic intraperitoneal chemotherapy potentially facilitates the safe retreatment of platinum therapy following this complication. We describe 3 ovarian cancer patients who were successfully retreated with carboplatin via hyperthermic intraperitoneal chemotherapy following hypersensitivity reaction.

Increased incidence of severe gastrointestinal events with first-line paclitaxel, carboplatin, and vorinostat chemotherapy for advanced-stage epithelial ovarian, primary peritoneal, and fallopian tube cancer.

OBJECTIVES: We sought to assess the response rate and toxicity of paclitaxel, carboplatin, andvorinostat primary induction therapy for the treatment of advanced-stage ovarian carcinoma. METHODS: Patients were treated with 6 cycles of weekly paclitaxel (80 mg/m), carboplatin (6 times area under the curve), and vorinostat (200 mg) every 28 days according to an institutional review board-approved protocol. The subjects were eligible for response evaluation; in patients who achieved stable disease or better following the conclusion of primary induction chemotherapy, they were subsequently treated with a planned 12 cycles of paclitaxel (135 mg/m) and vorinostat (400 mg) maintenance chemotherapy every 28 days. RESULTS: Eighteen patients received a combined 90 cycles (median, 6 cycles; range, 1-6 cycles) of primary induction chemotherapy. Of the 18 subjects, 7 demonstrated a complete response, and 2 subjects exhibited a partial response (a total response rate of 50.0%). Eight patients also received a combined total of 50 cycles (median, 5 cycles; range, 1-12 cycles) of consolidation therapy. Grade 3/4 neutropenia and thrombocytopenia were observed in 9 (56.3%) and 2 (12.5%) patients. One patient (6.3%) developed grade 3 anemia, and another (6.3%) manifested a grade 3 neuropathy. Remarkably, we observed a significant gastrointestinal event (eg, bowel anastomotic perforation) in 3 patients, which effectuated the study's closure. CONCLUSIONS: Because the current study was prematurely terminated, we cannot derive a conclusive assessment regarding the efficacy of this treatment. Nevertheless, the high incidence of severe gastrointestinal toxicity warrants further consideration when using vorinostat in the adjuvant setting for patients who have undergone a bowel resection as part of their initial tumor debulking.

Acute and delayed complications from surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer.

OBJECTIVES: This retrospective study assessed the number and type of complications following surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer. METHODS: Endometrial cancer patients who received surgery and postoperative radiotherapy (pelvic radiotherapy and/or vaginal brachytherapy) from April 1997 until October 2010 were evaluated. Short-term (≤6 months) and long-term (>6 months) complications (e.g., genitourinary/gastrointestinal complications) were comprehensively reviewed. RESULTS: We identified 109 high-risk endometrial cancer patients who completed adjuvant radiotherapy following either a total abdominal hysterectomy (TAH; n = 53) or minimally invasive hysterectomy (MIS; n = 56). The combined impact of surgery and radiotherapy on complication type did not reach statistical significance (p > 0.05). However, surgery type and the development of a complication were significantly related (p < 0.001). The MIS patients developed complications at a more accelerated rate compared to the TAH patients (21 vs. 45 months), although the incidence of toxicity of grade 3 or 4 was much higher in the TAH group. CONCLUSIONS: The impact of MIS and adjuvant radiotherapy may have adversely affected the development of complications compared to TAH patients who received adjuvant radiotherapy, although higher-grade patient toxicity was more prevalent in the TAH group.

The prognostic significance of optimal debulking in the setting of a complete clinical response for advanced ovarian carcinoma patients receiving maintenance chemotherapy.

AIM: We investigated if optimal surgical debulking increases tumor responsiveness to maintenance chemotherapy and improves survival in advanced ovarian cancer patients who previously attained a clinical complete response (CCR) to primary chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed 75 advanced ovarian cancer patients, of whom 43 and 32 underwent optimal versus suboptimal cytoreduction, respectively. All patients exhibited a CCR following 6 cycles of paclitaxel and carboplatin and subsequently received maintenance chemotherapy (paclitaxel 135 mg/m(2); q21 days). RESULTS: The median progression free survival (PFS) for the optimally debulked patients was 35 months, compared to 20 months for the suboptimal population (P = 0.003). Moreover, a Cox model analysis revealed that an increased number of maintenance chemotherapy cycles and optimal surgical reduction significantly correlated with favorable patient PFS (P < 0.001). In regard to overall survival (OS), the patients who had optimal cytoreductive surgery exhibited improved OS results compared to the sub-optimal surgery group (42 vs. 27 months; P < 0.001). However, a Cox model analysis indicated that a greater number of maintenance chemotherapy cycles was a surrogate marker for improved OS (P < 0.001), but surgery type was not (P > 0.05). Duration of overall patient follow-up exceeds 41 months. CONCLUSION: In advanced ovarian cancer patients who achieve a CCR following induction chemotherapy, optimal cytoreduction may confer a greater clinical benefit from a maintenance approach compared to suboptimal cytoreduction.

A pilot study evaluating a novel regimen comprised of carboplatin, paclitaxel, and bevacizumab for advanced-stage ovarian carcinoma.

OBJECTIVES: The purpose of this study was to assess the toxicity, progression-free survival, and response rate of advanced stage ovarian carcinoma patients treated with a novel regimen comprising paclitaxel, carboplatin, and bevacizumab. METHODS: All eligible patients were treated with intravenous paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (area under the curve, 5) on day 1; and bevacizumab (10 mg/kg) on days 1 and 15; Q28 days for 6 cycles. Bevacizumab was administered during cycles 2 through 6. RESULTS: Twenty patients received a combined total of 102 cycles of primary induction chemotherapy (median, 6; range, 2-6) and were evaluable for toxicity assessment. Six (5.9%) cycles were associated with grades 3 and 4 neutropenia, which resulted in the removal of 2 patients. Only 1 (0.98%) cycle was associated with grade 3 thrombocytopenia. Moreover, one patient developed a colorectal fistula and was subsequently removed from the study. Grade 3 hypertension was encountered and successfully managed in 3 participants. In the group of 13 patients who were evaluated for response, the overall response rate was 61.6% (30.8% complete response). Four patients exhibited stable disease, and 1 patient had progressive disease. The patient group's mean progression-free survival was 5.8 months. CONCLUSIONS: The tolerable hematologic toxicity and reasonable response rate after paclitaxel, carboplatin, and bevacizumab suggest that this regimen has moderate activity and can be safely administered to an advanced-stage ovarian carcinoma population. We were further encouraged by the reasonable incidence of hypertension. However, because 4 patients were removed from the study because of either grade ≥ 2 neutropenia or thrombocytopenia, we suggest that colony-stimulating factors and cautious patient observation should be considered with this regimen.

Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially confers significant survival benefits in the management of ovarian cancer although the long-term data remain scant. We sought to compare the survival rates of advanced stage ovarian cancer patients who were treated with primary induction therapy alone or in conjunction with consolidation HIPEC. METHODS: 69 ovarian cancer patients who underwent surgery and completed their primary induction chemotherapy were treated with consolidation carboplatin (AUC 10) based HIPEC and compared to a historical cohort that received surgery and primary chemotherapy alone (n = 69). The demographic and clinical characteristics on which we were primarily focused, included patient age, body mass index, surgery and pathology data, chemotherapy regimen, toxicity, and progression free/overall survival. RESULTS: The two patient groups' demographic and clinical characteristics were similar (P > 0.05). Progression-free survival was significantly more pronounced in the HIPEC (25.1 months) patients compared to the control group (20 months) (P = 0.024) and there was a decreased risk of disease progression accorded to the patients treated with HIPEC (HR 2.1028; 95% CI 1.2941-3.4167; P = 0.0027). However, we did not discern any HIPEC related overall survival advantages (P = 0.29). CONCLUSIONS: The results from our ovarian cancer study suggest that adjunctive HIPEC proffers a significant progression-free survival advantage and a decreased risk for disease progression. There was, however, no overall survival advantage discerned by the HIPEC group. We also recognize that HIPEC remains controversial, and thus randomized studies evaluating HIPEC compared to standard chemotherapy in the management of ovarian cancer are warranted.

Lower-extremity lymphedema following management for endometrial and cervical cancer.

BACKGROUND: Despite the alleged benefits conferred by a lymphadenectomy in the management of gynecologic malignancies, there are concerns regarding the development of postoperative lower-extremity lymphedema. The purpose of this study was to identify the incidence of lymphedema and associated risk factors in accordance with surgical staging during the management of endometrial and cervical cancer. METHOD: We conducted a 5-year review of all endometrial and cervical cancer patients who underwent a lymphadenectomy. The subjects' demographics, medical co-morbidities, diagnosis, surgical treatment, inclusion of adjuvant radiotherapy and incidence of lower-extremity lymphedema were noted. RESULTS: We identified 165 (135 endometrial cancer and 30 cervical cancer) subjects. Positive pelvic and para-aortic lymph nodes were present in 21 (12.7%) and 10 patients (6.1%), respectively. In the entire population, 6 (3.6% incidence) subjects developed post-operative lymphedema. Supplementary analyses revealed that a BMI >35 kg/m(2) and possessing numerous (≥3) co-morbidities significantly correlated with the manifestation of lower-extremity lymphedema. CONCLUSION: In the current investigation, we observed a reasonably low, overall incidence of postoperative lower-extremity lymphedema. Nevertheless, when evaluating the potential for lymphedema in patients for whom a lymphadenectomy is indicated, specific risk factors should be considered in an effort to attenuate the development of this morbid condition.

Survival rate comparisons amongst cervical cancer patients treated with an open, robotic-assisted or laparoscopic radical hysterectomy: A five year experience.

BACKGROUND: The purpose of this retrospective study was to assess the 5-year survival outcomes of cervical cancer patients who underwent an, open radical hysterectomy (ORH), robotic-assisted radical hysterectomy (RRH) or laparoscopic radical hysterectomy (LRH) for the treatment of their disease. METHOD: We conducted a review of all cervical cancer patients who were managed with an ORH, RRH or LRH. RESULT: Forty-nine patients were treated with LRH, 58 were managed via RRH and 39 patients underwent an ORH. The LRH (1.78 h) patients had a significantly shorter operative duration than the RRH (2.88 h) and ORH (2.39 h) subjects (p < 0.001). Blood loss was the highest in the ORH (475 cc) group (RRH = 207 cc and LRH = 312 cc) (P < 0.001). Moreover, the ORH (5.04 days) patients had a significantly longer hospital stay than the LRH (2.95 days) and RRH (2.50 day) subjects (P < 0.001). Kaplan-Meier survival analysis revealed a progression free survival (PFS) rate of 84.6% for the ORH group, 89.8% for the LRH group and 89.7% for the RRH patients (P = 0.271) at 60 months; overall survival was 92.3% for the ORH group, 95.9% for the LRH group and 96.6% for the RRH patients (P = 0.80). CONCLUSION: The results from this study suggest that, irrespective of operative approach, patients who underwent a radical hysterectomy for early stage cervical cancer attained similar 5-year disease free and overall survival outcomes.

Dramatically reduced incidence of vaginal cuff dehiscence in gynecologic patients undergoing endoscopic closure with barbed sutures: A retrospective cohort study.

INTRODUCTION: This retrospective study documented the rate of vaginal cuff dehiscence (VCD) in a large series of gynecologic patients who were treated with an endoscopic (robotic-assisted or laparoscopic) hysterectomy that incorporated either delayed absorbable monofilament barbed or vicryl running sutures. METHOD: We sought to discern any prognostic associations between operative variables (e.g., closure type (barbed or vicryl sutures), endoscopic approach (robotic-assisted or laparoscopic), and energy source (Harmonic Ace Shears or monopolar/bipolar electro-surgery)) and the risk for VCD via patient chart review. Statistical evaluation was comprised of univariate analyses and multiple regression. RESULTS: We identified 1876 subjects; there were 14 cases (0% with barbed suture and 0.99% with vicryl suture) of VCD (an overall incidence of 0.75%), nearly all of which were associated with a robotic-assisted hysterectomy involving vicryl sutures (p = 0.034). However, the type of endoscopic surgery (P = 0.11) and energy source (P = 0.28) were not significant prognostic factors. The VCD patients' exhibited a median duration of 47 days (range, 14-116) until the development of their condition. CONCLUSION: Vaginal cuff separation subsequent to laparoscopic closure is a rare occurrence. While our incidence of VCD was low and comparable to other reported rates in the literature, we did not observe any cases of VCD following laparoscopic hysterectomy performed with barbed suture closure.

A comparison of open surgery, robotic-assisted surgery and conventional laparoscopic surgery in the treatment of morbidly obese endometrial cancer patients.

BACKGROUND AND OBJECTIVES: The intent of this retrospective study was to assess the operative outcomes of morbidly obese endometrial cancer patients who were treated with either open surgery (OS) or a minimally invasive procedure. METHODS: Morbidly obese (body mass index [BMI] > 40 kg/m(2)) patients with endometrial cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or conventional laparoscopic surgery (LS) were eligible. We sought to discern any outcome differences with regard to operative time, perioperative complications, and hospital stay. RESULTS: Sixteen patients were treated with LS (BMI = 47.9 kg/m(2)), 13 were managed via RS (BMI = 51.2 kg/m(2)), and 24 underwent OS (BMI = 53.7 kg/m(2)). The OS (1.35 hours) patients had a significantly shorter operative duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a significantly longer hospital stay than the LS (2 days) and RS (2 days) patients (P = .002). CONCLUSION: In the present study, we ascertained that minimally invasive surgery was associated with longer operative times but lower rates of blood loss and shorter hospital stay duration compared with treatment comprising an open procedure.

A phase II study of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage primary epithelial ovarian, fallopian tube, or peritoneal carcinoma.

PURPOSE: Traditional dose-dense chemotherapy regimens for advanced stage ovarian cancer incorporate weekly paclitaxel on a 21-day cycle and are associated with favorable efficacy but high rates of neutropenia, thrombocytopenia, and anemia. The purpose of this phase II study was to assess the response rate and toxicity of modified dose-dense paclitaxel and every 4-week carboplatin for the treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma. METHODS: All eligible patients were treated with 6 cycles of intravenous dose-dense paclitaxel (80 mg/m²) days 1, 8, and 15 and carboplatin (AUC 5 or 6) Day 1 during a 28-day cycle in accordance with an IRB-approved protocol. Patients who had clinically defined stable disease or better with a CA-125 ≤ 35 U/ml following the completion of primary induction therapy were subsequently administered a planned 12 cycles of paclitaxel (135 mg/m²; every 21 days) consolidation therapy. RESULTS: Eighty-eight patients received at least 3 cycles of induction dose-dense chemotherapy, of whom 76 completed 6 cycles of chemotherapy; the overall response rate was 84.2 % (56.6 % complete response). Fifty-three patients received an aggregate 473 cycles (median = 9; range 1-12) of consolidation chemotherapy. Grade 3-4 hematological toxicity included neutropenia (22.7 %), thrombocytopenia (7.9 %), and anemia (1.1 %). Further, grade 3 neuropathy developed in one (1.1 %) patient. The patients' median disease-free survival and overall survival were 22.5 and 31.5 months, respectively. CONCLUSIONS: This phase II study suggests that first-line treatment comprising modified dose-dense paclitaxel and monthly carboplatin chemotherapy with paclitaxel consolidation therapy preserves the efficacy of traditional dose-dense chemotherapy, while minimizing hematologic toxicity.