NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer.

BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). RESULTS: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. CONCLUSIONS: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma.

COX-2 expression and survival in patients with locally advanced cervical cancer treated with chemoradiotherapy and celecoxib: a quantitative immunohistochemical analysis of RTOG C0128.

PURPOSE: This study aimed to measure expression of cyclooxygenase-2 (COX-2) and CD34 in pretreatment tumor biopsies from patients on the RTOG C0128 phase II study, and to correlate expression of these biomarkers, using quantitative immunohistochemistry, with clinical outcome parameters. METHODS AND MATERIALS: Pretreatment biopsies were placed into tissue microarrays. COX-2 and CD34 expression were measured using automated quantitative immunohistochemistry (AQUA®). Cox regression models and Fisher's exact test were used to explore associations between expression of the biomarkers and clinical end points. RESULTS: Eighty-four patients were accrued between 2001 and 2004; 78 were eligible and analyzable. Pathology specimen submission was optional; COX-2 expression was determined for 37 (47%) of patients, and CD34 scoring was determined for 34 (44%) of patients. Median follow-up was 44.5 months. In tumors where COX-2 data were available, 6 (16%) of 37 patients had local-regional failure; 4 of these patients had tumors with COX-2 scores below the AQUA® score median (hazard ratio, 0.39; 95% confidence interval, 0.07-2.16; P = 0.28). Of the 8 patients with disease-free survival failures, 5 had tumors with COX-2 levels below the median (hazard ratio, 0.49; 95% confidence interval, 0.12-2.04; P = 0.32). The 4 patients who died all had COX-2 levels below the median value. COX-2 levels below the median were associated with worse 2-year survival (Fisher's P = 0.046). There was no statistically significant association between CD34 status and clinical outcome. CONCLUSIONS: Low COX-2 expression measured by AQUA® was associated with worse overall survival in this subset of patients available for analysis from RTOG C0128. Application of AQUA® technology, in a larger study, will be required to definitively evaluate the association COX-2 with clinical outcome in cervical cancer.

The quality of cervical cancer brachytherapy implantation and the impact on local recurrence and disease-free survival in radiation therapy oncology group prospective trials 0116 and 0128.

PURPOSE: The objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128. METHODS: All enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival. RESULTS: Records for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11-6.45; P = 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05-5.93; P = 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18-4.41; P = 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08-3.92; P = 0.03). CONCLUSIONS: Assessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners.

Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: a Gynecologic Oncology Group study.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome. METHODS: Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400mg/m(2) followed by 250mg/m(2) on days 1, 8, and 15 in a 21day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry. RESULTS: Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable; 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio=1.76, 95% confidence interval=0.96-3.21). CONCLUSIONS: The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy.

Clinical trials in recurrent ovarian cancer.

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

A phase II evaluation of weekly gemcitabine and docetaxel for second-line treatment of recurrent carcinosarcoma of the uterus: a gynecologic oncology group study.

BACKGROUND: The objective of this study was to estimate antitumor activity and toxicity of weekly docetaxel and gemcitabine as second-line chemotherapy for patients with recurrent uterine carcinosarcoma. METHODS: Patients with recurrent carcinosarcoma of the uterus who had failed one regimen of chemotherapy, had a Gynecologic Oncology Group (GOG) performance status of 0-2 and had measurable disease were included. Treatment consisted of gemcitabine 600 mg/m(2) and docetaxel 35 mg/m(2) intravenously on days 1, 8 and 15 of a 28-day cycle until disease progression or intolerable adverse effects. This study employed an optimal but flexible two-stage design with an early stopping rule. If more than 3 out of 22-24 or more than 4 out of 25-29 patients responded, accrual to the second stage was to be initiated. RESULTS: Twenty-eight patients were enlisted. Three patients were not eligible after pathology review. One patient was never treated. Twenty-four patients were evaluable. Nine patients had previous radiation therapy. There were no complete responses. Partial responses were seen in two patients (8.3%), stable disease in eight (33.3%) and progressive disease in 12 patients (50%). Two patients were not evaluable (8.3%). The median progression-free survival was 1.8 months. The median survival was 4.9 months. The treatment caused myelosuppression, mainly neutropenia, but also thrombocytopenia and anemia. Dose modifications became necessary in the majority of patients. In five patients, treatment was discontinued due to toxicity. CONCLUSIONS: This regimen of docetaxel and gemcitabine is not active in patients with recurrent carcinosarcoma of the uterus as second-line chemotherapy.

Hyperthermic intraperitoneal chemotherapy in ovarian cancer: first report of the HYPER-O registry.

INTRODUCTION: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC). METHODS: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded. RESULTS: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6 degrees C (median, 41.9 degrees C) for inflow and 36.9 to 42.9 degrees C (median, 41 degrees C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

Comparison of focus groups on cancer and employment conducted face to face or by telephone.

Findings from telephone focus groups have not been compared previously to findings from face-to-face focus groups. We conducted four telephone focus groups and five face-to-face focus groups in which a single moderator used the same open-ended questions and discussion facilitation techniques. This comparison was part of a larger study to gain a better understanding of employment experiences after diagnosis of gynecologic cancer. Offering the telephone option made it easier to recruit women from rural areas and geographically distant cities. Interaction between participants occurred in both types of focus group. Content analysis revealed that similar elements of the employment experience after cancer diagnosis were described by telephone and face-to-face participants. Participants disclosed certain emotionally sensitive experiences only in the telephone focus groups. Telephone focus groups provide useful data and can reduce logistical barriers to research participation. Visual anonymity might help some participants feel more comfortable discussing certain personal issues.

Employment and quality of survivorship among women with cancer: domains not captured by quality of life instruments.

BACKGROUND: Many quality of life instruments assess the amount of paid work in combination with role function at home in the same items and do not specifically assess social support in the workplace. The goal of this study was to obtain women's views on the relationship between employment and health-related quality of life. METHODS: A focus group and questionnaire study was conducted among 73 women with gynecologic cancer who were employed at diagnosis and 25 people who provided them with psychosocial support. RESULTS: The women held a variety of blue collar and white collar jobs at diagnosis. Employment provided a strong sense of accomplishment and a welcome distraction during treatment. The employment experience was described as distinct from role function at home. No one equated working more hours with better quality of life. Social support at work could be poor at the same time that support from family and friends grew stronger. CONCLUSIONS: The contribution to their quality of life that cancer survivors feel they receive from employment may not be linearly related to the quantity of their role function in the workplace. Employment-related items could be useful as an adjunct to standard quality of life measures.

Cancer-related tasks involving employment: opportunities for clinical assistance.

Many cancer survivors experience unmet psychosocial needs related to their jobs, and women often fare worse than men in this regard. However, little research exists on ways to assist patients with cancer in preventing or managing common job problems. We conducted focus groups and a survey among 73 women who were employed at the time of presentation of a gynecologic cancer. We compared the findings with existing recommendations and professional standards for occupational rehabilitation. Participants described different cancer-related employment tasks in three time periods: just after diagnosis, during primary treatment, and after primary treatment is completed. The more difficult tasks included communicating with supervisors and coworkers, determining company policies, applying for employer-sponsored benefits, handling finances, managing symptoms on returning to work, finding effective solutions to cancer-related job problems, leaving the job with dignity if too sick or if the job ended, and making career plans. The cancer care team may be able to help meet the psychosocial needs of employed cancer survivors by screening for job concerns, providing information, formulating a return-to-work plan, treating symptoms, consulting with professionals who have employment-related expertise, and giving other forms of assistance.

Symptom control in patients with recurrent ovarian cancer: measuring the benefit of palliative chemotherapy in women with platinum refractory/resistant ovarian cancer.

Most women with advanced ovarian cancer will relapse and subsequently develop platinum-resistant/refractory ovarian cancer. The benefit of treatment is currently based on objective response rates, which are a crude measure of benefit. It would be clinically meaningful if we were better able to measure the benefit of palliative therapy and, in particular, ascertain whether cancer-related symptoms improve with treatment and how this impacts on quality of life. This paper reviews the management of patients with platinum-resistant/refractory ovarian cancer and highlights the gaps in our knowledge and shortcomings with the current approaches to measure the benefit of treatment. The ultimate objective is to describe and encourage recruitment to the Gynecologic Cancer Intergroup study that has recently opened. This study will recruit a large number of patients from around the world in an effort to develop more robust instruments to measure the benefit of chemotherapy and to understand the impact of chemotherapy on symptom control and quality of life. In addition, this study will give us an insight into how all patients are managed rather than a select minority who are treated in clinical trials.

A Phase II study of acute toxicity for Celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG 0128.

PURPOSE: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. METHODS AND MATERIALS: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size > or =5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. RESULTS: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. CONCLUSIONS: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer.

Efficacy and patterns of failure for locally advanced cancer of the cervix treated with celebrex (celecoxib) and chemoradiotherapy in RTOG 0128.

PURPOSE: To determine the efficacy and patterns of initial failure for oral celecoxib, intravenous cisplatin, and 5-fluorouracil and concurrent pelvic radiotherapy in patients with locally advanced cancer of the cervix. METHODS AND MATERIALS: Patients were treated with concurrent 5-fluorouracil and cisplatin chemotherapy and pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at a dose of 400 mg twice daily for 1 year beginning on the first day of radiotherapy. The overall and disease-free survival rates were determined. RESULTS: A total of 84 patients were accrued, of whom 78 were eligible. The estimated 2-year disease-free survival and overall survival rate was 69% and 83%, respectively. Of the 78 patients, 24 had treatment failure: 3 with persistent local disease, 9 local only, 2 regional, 4 distant, 1 regional and distant, 1 local and distant, and 2 with local, regional, and distant disease, and 1 had died of cervical cancer without a reported site of first failure and 1 without evidence of disease. CONCLUSION: At 2 years, the estimated disease-free survival and overall survival rate for patients with advanced cervical cancer who underwent a combination of chemoradiotherapy and celecoxib treatment was 69% and 83%, respectively. Recurrent disease developed in 24 patients, and, of those patients, 18 had a component of locoregional failure as a site of first failure. Thus, locoregional control continues to be problematic after chemoradiotherapy as delivered in our study. The identification of more active biologically targeted therapies is warranted for the treatment of advanced cancer of the cervix.

Problems Experienced by Ovarian Cancer Survivors During Treatment.

OBJECTIVE: To identify problems at different treatment points (early treatment, mid-treatment, early posttreatment, and late posttreatment) among women with ovarian cancer. DESIGN: Longitudinal and cross-sectional study design. SETTING: An academic and community clinical cancer center in the Southeastern United States. PARTICIPANTS: Sixty-eight women with Stage I to IV ovarian cancer. METHODS: Variables assessed included reported problems (physical, psychosocial, pain, marital, medical interaction), social support, optimism, and responses to open-ended questions. Analysis involved mixed models for longitudinal repeated measures and unpaired t tests and content analysis to describe responses to open-ended questions. RESULTS: Physical and psychosocial problems were greatest during early treatment and decreased throughout the treatment trajectory. Women with greater levels of social support and optimism at baseline had fewer problems over time. Women who did not have trouble paying for basics had fewer problems related to pain and psychological problems. CONCLUSION: Problems across all domains must be addressed throughout the treatment trajectory, even after chemotherapy has ended. Nurses are well positioned to refer women appropriately to social workers and clinical navigators across all domains of care and should consider systematic assessment of patient-reported problems as a routine form of practice.

Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiation Without Brachytherapy in Low-resource Countries.

OBJECTIVE: To summarize the literature on options of management of patients treated for locally advanced cervical cancers with a specific focus on resource-constrained settings where brachytherapy is not available. MATERIALS AND METHODS: A Medline search was performed to summarize studies about treatment approaches including neoadjuvant chemotherapy, primary surgery for bulky cervical cancer, and chemoradiation followed by surgery. Summaries are by treatment approaches that are relevant to resource-constrained settings. RESULTS: There are a lack of studies performed on neoadjuvant chemotherapy in low-resource settings. Primary surgery followed by chemoradiation therapy for selected patients with bulky cervical cancer is a feasible option. The disadvantage is the potential increase in treatment complications. Chemoradiation without brachytherapy followed by surgery has been found to have equivalent outcomes and is associated with acceptable morbidity. CONCLUSIONS: In resource-constrained settings where brachytherapy is not available, performing radical hysterectomy after chemoradiation therapy without brachytherapy has been shown to produce equivalent outcomes. It seems reasonable to adopt a modified therapeutic protocol of chemoradiation followed by extrafascial hysterectomy as an alternative treatment option in low-resource countries where brachytherapy is not readily available.

Hematologic toxicity in RTOG 0418: a phase 2 study of postoperative IMRT for gynecologic cancer.

PURPOSE: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. METHODS AND MATERIALS: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m(2)). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. RESULTS: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥ 2 HT than did those with a dose of ≤ 34.2 Gy (74% vs 43%, P=.049). CONCLUSIONS: Pelvic IMRT with weekly cisplatin is associated with low rates of HT and high rates of weekly cisplatin use. The volume of bone marrow receiving 40 Gy and the median dose to bone marrow correlated with higher rates of grade ≥ 2 toxicity among patients receiving weekly cisplatin (cervical cancer patients). Evaluation and limitation of the volume of bone marrow treated with pelvic IMRT is warranted in patients receiving concurrent chemotherapy.

A phase II study of intensity modulated radiation therapy to the pelvis for postoperative patients with endometrial carcinoma: radiation therapy oncology group trial 0418.

PURPOSE: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. METHODS: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. RESULTS: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had an acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade ≥2 short-term bowel adverse events. CONCLUSIONS: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.

Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study.

PURPOSE: Platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen with established superiority based on a randomized phase III trial conducted through the Gynecologic Oncology Group. However, the toxicity, multiday schedule, and limited activity of this regimen support further development of novel regimens. Our primary objective was to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas. PATIENTS AND METHODS: Eligible patients had advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Patients received paclitaxel at 175 mg/m(2) intravenously (IV) over 3 hours plus carboplatin (area under the serum concentration-time curve = 6) IV over 30 minutes every 3 weeks until disease progression or until adverse effects occurred. Common Terminology Criteria for Adverse Events v3.0 was used to grade adverse events. RESULTS: Fifty-five patients were entered onto the study with nine being excluded from analysis, leaving 46 evaluable for analysis. Treatment was well tolerated with expected hematologic toxicity and minimal nonhematologic grade 4 toxicity (one cardiovascular and two pain) with 59% of patients completing six or more cycles of chemotherapy. The proportions of patients with confirmed complete and partial responses were 13% and 41%, respectively, resulting in a total overall response rate of 54% (95% CI, 37% to 67%). CONCLUSION: Paclitaxel plus carboplatin demonstrates antitumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials.

Restorative yoga for women with ovarian or breast cancer: findings from a pilot study.

Yoga has demonstrated benefit in healthy individuals and those with various health conditions. There are, however, few systematic studies to support the development of yoga interventions for cancer patients. Restorative yoga (RY) is a gentle type of yoga that has been described as "active relaxation." The specific aims of this pilot study were to determine the feasibility of implementing an RY intervention as a supportive therapy for women diagnosed with ovarian or breast cancer and to measure changes in self-reported fatigue, psychological distress and well-being, and quality of life. Fifty-one women with ovarian (n = 37) or breast cancer (n = 14) with a mean age of 58.9 years enrolled in this study; the majority (61%) were actively undergoing cancer treatment at the time of enrollment. All study participants participated in 10 weekly 75-minute RY classes that combined physical postures, breathing, and deep relaxation. Study participants completed questionnaires at baseline, immediately postintervention, and 2 months postintervention. Significant improvements were seen for depression, negative affect, state anxiety, mental health, and overall quality of life. Fatigue decreased between baseline and postintervention follow-up. Health-related quality of life improved between baseline and the 2-month follow-up. Qualitative feedback from participants was predominantly positive; relaxation and shared group experience were two common themes.

Cyclooxygenase inhibition and hyperthermia for the potentiation of the cytotoxic response in ovarian cancer cells.

OBJECTIVES: The progression of chemotherapy-resistant cancer confers poor prognosis and decreases overall survival in ovarian cancer patients. Adjuvants to traditional chemotherapy regimens have become attractive modalities for the clinical treatment of refractory or resistant ovarian cancer. We evaluated whether the addition of NSAID to hyperthermic chemotherapy would increase cytotoxicity in cisplatin- and taxane-treated ovarian cancer cells. METHODS: Western blot analysis was utilized to determine COX-2 protein expression levels in the 2008, cisplatin-sensitive, and C13*, cisplatin-resistant, cell lines. PGE2 levels were determined and analyzed as a function of cyclooxygenase activity by LC/MS/MS. Cells were treated with cisplatin, docetaxel or paclitaxel in combination with either NS-398 or sulindac sulfide at 37 degrees C, 41 degrees C or 43 degrees C. Cell viability was determined by a MTS cell proliferation assay. RESULTS: Both cell lines expressed COX-2 protein, and NS-398 and sulindac sulfide effectively blocked PGE2 production. The addition of a NSAID to cisplatin treatment in 2008 and C13* cells offered enhanced cytotoxicity and this effect was further enhanced at 41 degrees C. In docetaxel-treated 2008 cells, both NS-398 and sulindac sulfide offered enhanced cell kill; however, this result was not observed in paclitaxel-treated cells. Hyperthermia appeared to play no additional role in taxane cytotoxicity enhancement, however no antagonism was detected. CONCLUSIONS: Our results suggest that the combination treatment (cisplatin or docetaxel in combination with NSAID) cause a dose-dependent enhancement of cytotoxicity. Hyperthermia may improve the results of intraperitoneal cisplatin therapy, thus warranting further evaluation in clinical studies.