Advanced endometrial cancer: is lymphadenectomy necessary or sufficient?
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Endometrial Neoplasms↗
Biomedical subjects
David Scott Miller
Publications and source records attributed to David Scott Miller.
Hormonal therapy in epithelial ovarian cancer.
The ovary is an endocrine and end organ. Hormones and their receptors have been associated with ovarian cancer and may be related to its causation. Some data suggest that hormonal therapies may have an effect on ovarian cancer in palliative settings. The most well studied anticancer drugs are tamoxifen, megestrol acetate, medroxyprogesterone acetate, leuprolide acetate, anastrozole and letrozole. Presently, no hormonal therapy is approved by the US FDA for the treatment of any type of ovarian malignancy or is listed as an active agent by any of the authoritative compendia. Owing to the endocrine associations with ovarian cancer, the minimal side effects of hormonal therapy and the demonstrated activity of hormonal therapies in other endocrine organ-associated malignancies, further study of hormonal therapies for ovarian cancer is warranted.
Antineoplastic Agents, Hormonal↗
Phase II evaluation of 9-aminocamptothecin (9-AC, NSC #603071) in platinum-resistant ovarian and primary peritoneal carcinoma: a Gynecologic Oncology Group Study.
OBJECTIVE: To estimate the antitumor activity of 9-aminocamptothecin (9-AC) in patients with recurrent platinum-"resistant" ovarian cancer; and to determine the nature and degree of toxicity of 9-AC in this cohort of patients. METHODS: A multicenter phase II study was conducted by the Gynecologic Oncology Group (GOG). Patients were to receive 9-AC (colloidal dispersion) 25 microg/m(2)/h (600 microg/m(2)/day) IV over 120 h (5 days) beginning days 1 and 8. Dose adjustment was permitted for toxicity. This schedule was repeated every 21 days until disease progression or unacceptable adverse events. Hematopoietic growth factor support was used as necessary. RESULTS: From January 1999 to December 2000, 29 member institutions of the GOG enrolled 58 patients. Two patients received no therapy; thus, 56 (97%) were evaluable. Median age was 61 (range: 33-81) years. A median of four (range: 1-32) courses of 9-AC was administered. The most frequent grade 3 or 4 toxicities were neutropenia in 46%, leukopenia in 37%, gastrointestinal in 29%, anemia in 25%, and thrombocytopenia in 21%. There was one possible treatment-related death. There were four (7%) complete and four (7%) partial responses, for an overall response rate of 14%. Eighteen (32%) patients had stable disease, 22 (39%) progressed, and response could not be assessed in 8 (14%). CONCLUSION: The 9-AC at this dose and schedule showed limited activity comparable to that seen with other agents in platinum-resistant ovarian or primary peritoneal cancer.
Adult↗
Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6-12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study.
PURPOSE: A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. EXPERIMENTAL DESIGN: Patients were treated with a daily starting dose of 2500 mg/m2/day (divided in two doses given every 12 h) for 14 days of each 21-day cycle. Genotyping in the 5' and 3' ends of TS was performed in DNA from 23/23 pre-treatment blood specimens. Relative gene expression of TS, DPD, and TP was quantified in 18/21 paraffin-embedded tumor specimens. RESULTS: Of the 27 patients enrolled on study, 2 were never treated leaving 25 patients evaluable. Two patients (8.0%) achieved a partial response, 13 (52%) exhibited stable disease, 5 (20%) displayed increasing disease, and response could not be assessed in 5 (20%). The median time to progression and survival was 3.9 and 21.2 months, respectively. The most common serious toxicities were nausea/vomiting, gastrointestinal, and dermatological. There was one treatment-related death. TS expression was associated with severe nausea/vomiting (P = 0.039), but not with other severe toxicities. TS genotype or expression of DPD or TP was not associated with any of the severe toxicities. CONCLUSIONS: Based on the low response rate, this trial was closed after the first stage of accrual, the drug was not selected for further study in this patient population, and biomarker associations with response could not be assessed.
Adult↗
Phase II evaluation of topotecan in carcinosarcoma of the uterus: a Gynecologic Oncology Group study.
OBJECTIVES: To estimate the antitumor activity of topotecan in patients with persistent or recurrent carcinosarcoma (malignant mixed mullerian tumors) of the uterus and to determine the nature and degree of toxicity of topotecan in this cohort of patients. MATERIALS AND METHODS: Eligible patients had measurable advanced or recurrent carcinosarcoma of the uterus. Topotecan at a target dose of 1.5 mg/m(2) was administered IV daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. RESULTS: Twenty-seven member institutions entered 51 patients. Of the patients entered, 48 were eligible. Patient characteristics included a median age of 65, with 33% having prior radiation and 92% having prior chemotherapy. Twenty-six patients (54%) had a performance status (PS) of 0, 18 (38%) had a PS of 1, and four (8%) had a PS of 2. Patients received from 1 to 21 (with a median of 2) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 35 (73%) patients, leukopenia in 14 (29%), and thrombocytopenia in 10 (21%). Three (6%) patients developed neutropenic sepsis and died shortly after their first treatment cycle. There were five (10%) complete responses; 13 (27%) patients maintained stable disease, 26 (54%) experienced increasing disease, and reassessment did not occur in four (8%). CONCLUSION: Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent uterine carcinosarcoma previously treated with chemotherapy.
Adult↗
A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies.
BACKGROUND: The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS: During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 microg (n = 122) or at a weight-based dose of 4.5 microg/kg (n = 120) once weekly until they achieved a hemoglobin concentration > or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS: Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS: Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.
Aged↗
Other primary malignancies in patients with uterine corpus malignancy.
OBJECTIVE: The purpose of this study was to determine the occurrence of multiple primary malignancies in patients with uterine corpus malignancy. STUDY DESIGN: We conducted a tumor registry search and a medical record review. RESULTS: Uterine corpus malignancy was reported in 1505 of 25605 women (6%) in the registries, of which 131 of 1505 women (9%) had multiple primary malignancies. Patients with uterine corpus malignancy with multiple primary malignancies were more likely to have had primary malignancies of the ovary (relative risk, 10; 95% CI, 6.2-17) and colon (relative risk, 2; 95% CI, 1.0-4.3) and less likely to have had primary malignancies of the cervix (relative risk, 0.4; 95% CI, 0.17-0.97) compared with women who had only one primary malignancy. A family history of malignancy was reported in only 44% of the patients with uterine corpus malignancy with multiple primary malignancies and 32% of those patients whose multiple primary malignancies were from the ovary or colon. CONCLUSION: The development of multiple primary malignancies in patients with uterine corpus malignancy may indicate an inherited predisposition, especially in those patients whose multiple primary malignancies include the ovary or colon. That predisposition may not be detected by routine family history.
Adult↗
Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.
PURPOSE: Vinorelbine is being explored by the Gynecologic Oncology Group (GOG) for its possible use in advanced or recurrent squamous cell carcinoma of the uterine cervix. The objective of this Phase II trial was to evaluate a days 1 and 8 every-21-days schedule and determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients with measurable disease and satisfactory baseline bone marrow, liver, and kidney functions were treated with vinorelbine 30 mg/m(2) given on days 1 and 8 every 21 days. A two-stage sampling design was used, proceeding to a second stage accrual if sufficient activity was documented in the first 25 patients. RESULTS: The study did proceed to the second stage and accrued 44 patients. There were six objective responses (one complete, five partial) for a response rate of 13.7% (95% confidence interval: 5.2-27.4%). There were three patients with response in extra-pelvic sites (including the complete response) and three with response in the pelvis. The overall frequency of grades 3 and 4 neutropenia was 41%, whereas neuropathy was reported in 27% and was severe in three. Treatment-related pain, very severe in two instances, was also reported in 27%. CONCLUSION: Vinorelbine has moderate activity in a pretreated population with squamous cell carcinoma of the cervix. Accordingly, vinorelbine in this days 1 and 8 schedule is being studied further in combination with cisplatin by the GOG.
Adult↗
Phase II evaluation of three-day topotecan in recurrent platinum-sensitive ovarian carcinoma: a gynecologic oncology group study.
BACKGROUND: Topotecan, administered intravenously at a dose of 1.5 mg/m(2) per day for 5 days every 21 days, is an established regimen in the treatment of recurrent ovarian carcinoma. Alternate dosing strategies have sought to improve toxicity. The authors evaluated the tolerability and antitumor activity of a 3-day topotecan regimen. METHODS: A multicenter Phase II study, which included patients with platinum-sensitive ovarian carcinoma, was conducted. Patients were to receive an intravenous dose of topotecan of 2.0 mg/m(2) per day for 3 days every 21 days until disease progression or unacceptable toxicity occurred. Doses were modified in 0.25-mg/m(2) increments based on tolerability. Granulocyte-colony-stimulating factor support was used as necessary. RESULTS: From February to June 2000, 30 patients were enrolled. Their median age was 56 years (range, 41-81 years). Twenty-nine patients were evaluable for toxicity and efficacy. A median of 5 courses (range, 1-11 courses) of topotecan was administered. Eighteen of 30 (60%) patients experienced Grade 4 neutropenia. There was one report each of Grade 4 thrombocytopenia, anemia, and gastrointestinal toxicity (grading performed according to National Cancer Institute Common Toxicity Criteria). Ten patients developed Grade 3 leukopenia and 9 had Grade 3 neutropenia. Serious nonhematologic events were rare. There were 2 (7%) complete and 2 (7%) partial responses, for an overall response rate of 14%. Sixteen (55%) patients had stable disease and 9 (31%) experienced disease progression. CONCLUSIONS: A 3-day regimen of topotecan at a dose of 2.0 mg/m(2) per day was generally well tolerated, although the response rate was lower than that for the standard 5-day schedule.
Adult↗
Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy. A case report and review of the literature.
Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45-negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM.
Diagnosis, Differential↗
Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study.
OBJECTIVE: Because of preliminary observations favoring the use of mitomycin, doxorubicin, and cisplatin (MAP) chemotherapy in leiomyosarcomas, the Gynecologic Oncology Group (GOG) decided to conduct a phase II clinical trial of this combination regimen in patients with advanced disease. METHODS: Patients with histologically confirmed uterine leiomyosarcoma who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Mitomycin 8 mg/m(2) and doxorubicin 40 mg/m(2) were each given by iv injection followed immediately by cisplatin 60 mg/m(2) in 1 liter of 0.45% saline plus mannitol 25 g. Patients who remained free from tumor progression or intolerable toxicity received at least three, to a maximum of six, cycles of MAP. RESULTS: Forty-one patients were registered, of whom 4 were determined ineligible (wrong cell type, 2; wrong site of origin, 1; inadequate pathology material, 1). Thirty-five of the 37 were evaluable for response after receiving from one to six (median three) cycles of MAP. Three patients (9%) achieved a complete response and 5 (14%) exhibited a partial response. The most common adverse effects were leukopenia (33 patients) and thrombocytopenia (30 patients). Pulmonary toxicity was seen in 10 patients and was a factor in the clinical deterioration and death of 2. CONCLUSION: MAP is active against advanced uterine leiomyosarcomas, but not remarkably so. Despite its low therapeutic index, this novel, possibly interactive, combination may serve as a forerunner to regimens that more efficiently exploit the enhancement of sarcoma cell kill under hypoxic conditions.
Antineoplastic Combined Chemotherapy Protocols↗
A phase II trial of topotecan in patients with advanced, persistent, or recurrent endometrial carcinoma: a gynecologic oncology group study.
OBJECTIVE: To estimate the antitumor activity of topotecan in women with advanced, persistent, or recurrent endometrial carcinoma previously treated with chemotherapy, and to determine the nature and degree of toxicity of topotecan in this cohort of patients. MATERIALS AND METHODS: Eligible patients were those who had failed one prior chemotherapy regimen. Topotecan 0.5 to 1.5 mg/m(2) was administered iv daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. RESULTS: Of 29 patients entered, 28 were evaluable for toxicity and 22 were evaluable for response. Patient characteristics included a median age of 65, with 41% having prior radiation and 14% having prior hormonal therapy. Nine patients (41%) had a performance status (PS) of 0, 11 (50%) had a PS of 1, and 2 (9%) had a PS of 2. Patients received from 2 to 11 (with a median of 4) courses of treatment. The most frequently observed grade 4 toxicities were neutropenia seen in 17 (61%) patients, leukopenia in 11 (39%), and thrombocytopenia in 7 (25%). Two deaths were considered potentially related to treatment. There was one (4.5%) complete and one (4.5%) partial response; 12 (55%) patients maintained stable disease and eight (36%) experienced increasing tumor. CONCLUSION: Topotecan at this dose and schedule does not appear to have major activity in patients with advanced or recurrent endometrial carcinoma previously treated with chemotherapy.
Adult↗