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ABSTRACT: Despite increased use of integrative medicine in cancer therapy, little data exist on its efficacy. This prospective, randomized, pilot trial sought to evaluate the feasibility of combined modality integrative medicine (CM-IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of life (QoL), chemotherapy toxicity and immunologic profiles.
Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those randomized to the experimental arm received hypnosis, therapeutic massage and healing touch with each cycle of chemotherapy. The control arm received chemotherapy without CM-IM. All patients completed QoL questionnaires prior to cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were measured. Statistical analysis was based on intent-to-treat. Student's t-test and Fischer's exact-test were used to determine differences.
Forty-three women enrolled. All women randomized to CM-IM were successfully treated. There were no statistical differences between the groups in age, stage, grade, histologic cell type, CA125 levels, or surgical cytoreductive status. There was no difference in overall QoL measurements. Re-hospitalization rates, treatment delays, anti-emetic use, and infection rates were similar. Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels. Women receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although this did not reach statistical significance.
Prospective clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated improvements in immunologic profiles warrant further investigation.
Gynecologic Oncology 08/2011; 123(2):346-50. · 3.89 Impact Factor
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ABSTRACT: (1) To determine the response rate of advanced, recurrent, or persistent carcinoma of the cervix to ifosfamide, paclitaxel, and carboplatin chemotherapy; (2) to determine the progression free interval and survival rate in patients treated with this regimen; (3) to describe the toxicities associated with this regimen; and (4) to evaluate the quality of life of patients while on treatment.
Eligible patients had histologically proven stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. Chemotherapy was given on day 1 of a 28-day cycle: mesna (600 mg/m(2)) prior to ifosfamide (2 g/m(2)), paclitaxel (175 mg/m(2)), carboplatin (AUC 5). Response rates were determined according to RECIST criteria. Toxicity was graded according the National Cancer Institute's common toxicity criteria. Quality of life measurements were obtained using the FACT-Cx.
Twenty-eight patients participated in this study, with 21 evaluable for response rate. Overall, 7 patients (33%) had a demonstrated objective response (4 complete responses, 3 partial responses). Stable disease was documented in 3 patients. The overall median survival for all patients was 10 months. Median progression free survival for evaluable patients was 5.0 months. Bone marrow suppression was the most common toxicity. There were no negative effects of this treatment regimen on quality of life assessments.
Ifosfamide, paclitaxel, and carboplatin is an effective regimen in treating advanced or recurrent carcinoma of the cervix and has an acceptable toxicity profile.
Gynecologic Oncology 02/2011; 120(2):265-9. · 3.89 Impact Factor
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Melissa A Geller,
Sarah Cooley,
Patricia L Judson, Rahel Ghebre,
Linda F Carson,
Peter A Argenta,
Amy L Jonson,
Angela Panoskaltsis-Mortari,
Julie Curtsinger,
David McKenna,
Kathryn Dusenbery,
Robin Bliss,
Levi S Downs,
Jeffrey S Miller
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ABSTRACT: Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer.
Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/μL blood 14 days after infusion, based on molecular chimerism and flow cytometry.
Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30-65) years. Mean NK cell dose was 2.16 × 10(7)cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion.
Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.
Cytotherapy 01/2011; 13(1):98-107. · 3.63 Impact Factor
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Melissa A Geller,
Joseph J Ivy, Rahel Ghebre,
Levi S Downs,
Patricia L Judson,
Linda F Carson,
Amy L Jonson,
Kathryn Dusenbery,
Rachel Isaksson Vogel,
Matthew P Boente,
Peter A Argenta
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ABSTRACT: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer.
Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS).
Forty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age=58 years (range: 21-81 years). 78% (32/41)=endometrioid histology. Stages=10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent=1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7-70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82-99%), at 3 years 90% (75-96%), and at 5 years 71% (45-86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72-94%), at 3 years 71% (51-83%), and at 5 years 64% (42-80%).
"Sandwiching" radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.
Gynecologic Oncology 01/2011; 121(1):112-7. · 3.89 Impact Factor
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Melissa A Geller,
Sarah Cooley,
Peter A Argenta,
Levi S Downs,
Linda F Carson,
Patricia L Judson, Rahel Ghebre,
Brenda Weigel,
Angela Panoskaltsis-Mortari,
Julie Curtsinger,
Jeffrey S Miller
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ABSTRACT: The primary objective was to study the antitumor activity of prolonged subcutaneous dosing of systemic 852A, a Toll-like receptor-7 agonist (TLR-7), in recurrent breast, ovarian and cervix cancer. Secondary objectives included assessment of safety and immune system activation.
Adults with recurrent breast, ovarian or cervix cancer failing multiple therapies received 0.6 mg/m(2) of 852A subcutaneously twice weekly for 12 weeks. Doses increased by 0.2 mg/m(2)/week to a maximum of 1.2 mg/m(2). Serum was collected to assess immune activation.
Fifteen patients enrolled: 10 ovarian, 2 cervix and 3 breast. Three completed all 24 injections. There were two grade 2 (decreased ejection fractions), nine grade 3 (1 cardiovascular, 1 anorexia, 3 dehydration, 2 infections, 2 renal) and two grade 4 (hepatic and troponin elevation) unanticipated toxicities. Cardiac toxicities included three cardiomyopathies (2 asymptomatic) and one stress-related non-ST elevated myocardial infarction. Five patients discontinued therapy due to possibly associated side effects. One who had stable disease (SD) following 24 doses received 17 additional doses. A cervix patient with SD following 24 doses received chemotherapy after progressing 3 months later, and remains disease free at 18 months. Immune activation, as evidenced by increased IP-10 and IL-1ra, was observed.
In this first human experience of a TLR-7 agonist delivered subcutaneously using a prolonged dosing schedule, 852A demonstrated sustained tolerability in some patients. Clinical benefit was modest, but immune activation was seen suggesting further study of antitumor applications is warranted. Because of cardiac toxicity; 852A should be used cautiously in heavily pretreated patients.
Cancer Immunology and Immunotherapy 12/2010; 59(12):1877-84. · 3.70 Impact Factor
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ABSTRACT: Effective patient -clinician communication at diagnosis is important, yet decreased provider time for face-to-face interactions makes traditional paradigms in cancer care difficult. We evaluated the effects of an educational video on patients' distress, cancer knowledge, coping skills and attitudes regarding learning about cancer at the time of ovarian cancer diagnosis.
An educational video was developed in which oncology professionals, women with ovarian cancer, and their relatives discussed cancer information and experiences. Women admitted for initial diagnostic surgical staging for ovarian cancer were randomized to the educational or placebo video. Before and after the video, patients completed measures of (1) ovarian cancer information, (2) emotional distress, (3) learning attitudes, and (4) coping self-efficacy. Outcomes were analyzed for differences in mean change between intervention and placebo groups using t-tests.
Fifty-nine subjects were randomized (30 intervention/29 placebo). The majority were advanced staged, white, insured, high school educated, employed, and rated their disease seriousness as high. Anxiety, general distress and cancer-specific distress were high. Pre-post video: distress and self-efficacy between groups were unchanged, intervention subjects answered more knowledge items correctly (p=0.0004) and developed more negative learning attitudes (p=0.037). Following the educational video, patients who developed more negative attitudes also had increased intrusive thinking (p=0.046), a sign of increased distress.
Video presentation of cancer-related information increases learning under conditions of high distress and disease threat however, it is not without risk for some. Differing information needs may affect women's emotional response under these conditions.
Gynecologic Oncology 11/2010; 119(2):370-5. · 3.89 Impact Factor
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ABSTRACT: We sought to evaluate the outcomes and feasibility associated with delivering sequential chemotherapy and radiation in advanced stage endometrial cancer.
We conducted a retrospective analysis of patients treated at the University of Minnesota with sequential chemotherapy and radiation for advanced stage endometrial cancer from 1999 to 2007. Inclusion criteria were endometrial cancer patients treated with comprehensive surgical staging followed by adjuvant therapy consisting of sequential chemotherapy, radiation, and consolidation chemotherapy in a "sandwich" fashion. Progression free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier (KM) method.
Twenty-three patients met entry criteria and were included in the analysis. The median age was 57 years (range 28-78). The majority of patients were stage III (78%) and the most common histologic type was serous (52%). The combination of a taxane and carboplatin was administered in 100% of cases. All planned cycles of chemotherapy were completed (100%) with the majority being prescribed six cycles (82%). Of the 23 patients, 5 progressed of which 3 died during the follow up period. The KM estimate of 1, 3, and 5 year PFS is 100%, 80%, and 74%, respectively. The KM estimate for 1, 3, and 5 year OS is 100%, 88% and 79%, respectively.
Adjuvant therapy delivered in a "sandwich" fashion was feasible, well-tolerated and resulted in excellent long-term progression free and overall survival. A prospective study is currently ongoing at our institution.
Gynecologic Oncology 04/2010; 118(1):19-23. · 3.89 Impact Factor
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Levi S Downs,
Patricia L Judson,
Peter A Argenta, Rahel Ghebre,
Melissa A Geller,
Robin L Bliss,
Matthew P Boente,
William A Nahhas,
Samir Z Abu-Ghazaleh,
M Dwight Chen,
Linda F Carson
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ABSTRACT: Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide.
Women were enrolled in this multicenter, prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible patients had recurrent epithelial ovarian carcinoma with measurable disease or elevated CA 125 values. Patients had received prior platinum-based chemotherapy. Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5 of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per day and then increasing the dose as tolerated. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. The chi-square test was used to assess differences in response and toxicity, and the log-rank test was used to compare Kaplan-Meier survival curves.
The analysis included 69 women (39 women in the control arm and 30 women in the thalidomide arm). Known prognostic factors, including platinum sensitivity, were represented equally in each arm. The median thalidomide dose was 200 mg per day. The overall response rate in the control arm was 21% (complete response [CR] rate, 18%; partial response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%; PR rate, 17%) (P= .03). The median progression-free survival for the control arm was 4 months compared with 6 months in the thalidomide arm (P= .02). The median overall survival was 15 months in the control arm and 19 months in the thalidomide arm (P= .67). Toxicities were similar between groups.
The addition of thalidomide to topotecan for the treatment of recurrent ovarian cancer appears to improve response rates, and the authors believe that it warrants study through larger phase 3 trials.
Cancer 02/2008; 112(2):331-9. · 4.77 Impact Factor
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ABSTRACT: To determine if pelvic examination affected management in patients undergoing first-line chemotherapy for ovarian cancer and to determine a threshold of change in tumor size reliably detectable by pelvic examination.
We reviewed 501 encounters among 47 women with ovarian cancer to see if pelvic examination prompted a management change. Clinicians then evaluated synthetic model "tumors" and were retested at intervals of 3-48 hours to determine change needed for reliable detection.
The median number of examinations was 3 during 8 cycles of chemotherapy. Fifteen examinations (10.5%) revealed palpable anomalies, attributable to known tumor in 10 instances. The most common events preceding management change were elevation in serum CA-125 (57%) or chemotherapy toxicity (20%). No changes were made based on pelvic examination alone. When assessing "tumor" volume in a model, estimates ranged from 33-309% of actual volume. Determination of volume change following a delay was poor. No reliable threshold of detection of volume change was established.
Pelvic examination findings rarely dictated management changes in this study. Further, our results call into question the potential of routine pelvic examination to add significantly to clinical management during initial treatment given the wide range of error in "tumor" size estimates.
The Journal of reproductive medicine 02/2008; 53(1):3-7. · 0.87 Impact Factor
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ABSTRACT: Brain metastasis from uterine cancer is a rare event. Consequently, the optimal management strategy is not defined. We reviewed our institution's experience with brain metastasis from endometrial cancer along with the extant medical literature to develop management recommendations.
Twenty patients with CNS metastasis were identified. Information regarding symptoms, treatment, and survival was collected. The Kaplan-Meier method was used to compare survival data.
The incidence of CNS metastasis was 0.97%. Median patient age at initial diagnosis of endometrial cancer was 62.0 years and 64.0 years at diagnosis of brain metastasis. Most patients initially presented with advanced FIGO stage: 9 stage IVB, 4 stage IIIC, 4 stage IIIA, 2 stage IB, and 1 stage IA. The median interval from diagnosis of endometrial cancer to diagnosis of brain metastasis was 11.5 months (range 0.6-73.6). Median survival after diagnosis of brain metastasis was 2.0 months (range 0.1-39.2). Improved survival was seen in patients treated with multimodal therapy compared to patients who only received whole brain radiotherapy (WBRT) (p=0.0001) or compared to patients who received no treatment (p=0.009). No difference in survival was seen between patients treated with WBRT versus no therapy. The survival advantage associated with multimodal therapy was also supported by case reports and case series in the literature.
Based upon the data presented along with the medical literature, multimodal therapy appears to improve the survival of patients with CNS metastasis from uterine cancer.
Gynecologic Oncology 11/2007; 107(1):79-85. · 3.89 Impact Factor
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ABSTRACT: Objective. The goal of treating recurrent ovarian cancer is disease control while minimizing toxicity. Fulvestrant, a novel estrogen receptor (ER) antagonist, has proven clinically beneficial and well-tolerated in treating recurrent breast cancer. Ovarian cancer often expresses ER and may respond to anti-estrogen therapy. We evaluated fulvestrant in women with recurrent ovarian or primary peritoneal cancer.Methods. Patients with ER-positive, multiply recurrent ovarian or primary peritoneal carcinoma and either measurable disease according to RECIST criteria or an abnormal and rising CA-125 were eligible for enrollment. Treatment consisted of single agent fulvestrant, 500 mg IM on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression. Disease response was assessed by monthly physical exams and CA-125 levels as well as CT scans bimonthly. The primary endpoint was clinical benefit (CB = complete response (CR) + partial response (PR) + stable disease (SD)) at 90 days.Results. Thirty-one women were enrolled and 26 women (median age of 61) met inclusion criteria and received at least one dose. Patients had received a median of 5 prior chemotherapeutic regimens (range: 2–13). We observed one CR (4%), one PR (4%), and 9 patients with SD (35%) using modified-Rustin criteria (CA-125 level). Using modified-RECIST criteria 13 patients (50%) achieved SD. The median time to disease progression was 62 days (mean 86 days). Grade 1 toxicity included headache (1 patient) and bromidrosis (2 patients).Conclusions. Fulvestrant is well-tolerated and efficacious. Objective response rates are low, but disease stabilization was common.
Gynecologic Oncology.
