41 results on '"Spicer, D. V."'
Search Results
2. Estrogens, Progestins, and Risk of Breast Cancer
- Author
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Pike, M. C., primary, Wu, A. H., additional, Spicer, D. V., additional, Lee, S., additional, and Pearce, C. L., additional
- Published
- 2007
- Full Text
- View/download PDF
3. Clinical characteristics of affected BRCA1 and BRCA2 mutation carriers in an underserved population.
- Author
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El-Masry, M., primary, Ricker, C., additional, Spicer, D. V., additional, and Tripathy, D., additional
- Published
- 2011
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- View/download PDF
4. Predictors of pathologic response and correlation with long-term outcomes in a trial of neoadjuvant concurrent paclitaxel radiation in locally advanced breast cancer (LABC).
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Adams, S., primary, Lymberis, S. C., additional, Chakravarthy, A. B., additional, Spicer, D. V., additional, Hochman, T., additional, Donach, M., additional, Goldberg, J. D., additional, Schneider, R., additional, Pietenpol, J. A., additional, and Formenti, S., additional
- Published
- 2010
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5. Five-year results of preoperative concurrent paclitaxel with radiation in locally advanced breast cancer (LABC).
- Author
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Formenti, S., primary, Adams, S., additional, Chakravarthy, A. B., additional, Lymberis, S. C., additional, Spicer, D. V., additional, Bauer, J. A., additional, Volm, M., additional, Roses, D., additional, Goldberg, J. D., additional, and Pietenpol, J. A., additional
- Published
- 2010
- Full Text
- View/download PDF
6. Estrogens, Progestins, and Risk of Breast Cancer.
- Author
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Conneely, O., Otto, C., Pike, M. C., Wu, A. H., Spicer, D. V., Lee, S., and Pearce, C. L.
- Abstract
Obesity is associated with a decreased risk of breast cancer in premenopausal women but an increased risk in postmenopausal women, an effect that increases with time since menopause. Analysis of these effects of obesity shows that there is a ceiling to the carcinogenic effect of estrogen on the breast; increases in nonsex hormone-binding globulin-bound estradiol (non-SHBG bound E2) exceeding approximately 10.2 pg/ml have no further effect on breast cancer risk; this ceiling is lower than the lowest level seen during the menstrual cycle. This suggests that the effects of menopausal estrogen therapy (ET) and menopausal estrogen-progestin therapy (EPT) on a woman's breast cancer risk will greatly depend on her body mass index (BMI; weight in kilograms/height in meters squared, kg/m2) with the largest effects being in slender women. Epidemiological studies confirm this prediction. Our best estimates, per 5 years of use, of the effects of ET on breast cancer risk is a 30% increase in a woman with a BMI of 20 kg/m2 decreasing to an 8% increase in a woman with a BMI of 30 kg/m2; the equivalent figures for EPT are 50% and 26%. The analysis of the effects of estrogen also shows that even reducing the dose of estrogen in ET and EPT by as much as a half will have little or no effect on these risks. Reducing the progestin dose is likely to significantly reduce the risk of EPT: this is possible with an endometrial route of administration. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
7. Hormonal contraception and chemoprevention of female cancers.
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Pike, M C, primary and Spicer, D V, additional
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- 2000
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8. Problems Involved in Including Women with Simple Hysterectomy in Epidemiologic Studies Measuring the Effects of Hormone Replacement Therapy on Breast Cancer Risk
- Author
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Pike, M. C., primary, Ross, R. K., additional, and Spicer, D. V., additional
- Published
- 1998
- Full Text
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9. A hormonal contraceptive approach to reducing breast and ovarian cancer risk: an update
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Pike, M C, primary, Daniels, J R, additional, and Spicer, D V, additional
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- 1997
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- View/download PDF
10. Experiments on proliferation of normal human breast tissue in nude mice do not show that progesterone does not stimulate breast cells.
- Author
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Pike, M C, primary, Ursin, G, additional, and Spicer, D V, additional
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- 1996
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- View/download PDF
11. Can Mammographic Densities Predict Effects of Tamoxifen on the Breast?
- Author
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URSIN, G., primary, PIKE, M. C., additional, SPICER, D. V., additional, PORRATH, S. A., additional, and REITHERMAN, R. W., additional
- Published
- 1996
- Full Text
- View/download PDF
12. BOOK REVIEW
- Author
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SPICER, D. V., primary
- Published
- 1994
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13. Changes in Mammographic Densities Induced by a Hormonal Contraceptive Designed to Reduce Breast Cancer Risk
- Author
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Spicer, D. V., primary, Ursin, G., additional, Parisky, Y. R., additional, Pearce, J. G., additional, Shoupe, D., additional, Pike, A., additional, and Pike, M. C., additional
- Published
- 1994
- Full Text
- View/download PDF
14. Tamoxifen and Estrogen Replacement Therapy as Agents of Disease Prevention
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SPICER, D. V., primary, PIKE, M. C., additional, HENDERSON, B. E., additional, and GROSHEN, S., additional
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- 1991
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15. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks.
- Author
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Roberts, John D., Shibata, Stephen, Spicer, Darcy V., McLeod, Howard L., Tombes, Mary Beth, Kyle, Brenda, Carroll, Mary, Sheedy, Beth, Collier, Mary A., Pithavala, Yazdi K., Paradiso, Linda J., Clendeninn, Neil J., Roberts, J D, Shibata, S, Spicer, D V, McLeod, H L, Tombes, M B, Kyle, B, Carroll, M, and Sheedy, B
- Subjects
DRUG metabolism ,CANCER treatment ,CLINICAL drug trials ,CANCER patients ,CANCER ,THERAPEUTICS ,ANTINEOPLASTIC agents ,ENZYME inhibitors ,CLINICAL trials ,COMPARATIVE studies ,DRUG administration ,GLUTAMIC acid ,RESEARCH methodology ,HETEROCYCLIC compounds ,MEDICAL cooperation ,RESEARCH ,TRANSFERASES ,TUMORS ,EVALUATION research - Abstract
Purpose: To identify a recommended phase II dose for the second generation glycinamide ribonucleotide transformylase (GARFT) inhibitor, AG2034, administered by intravenous bolus every 3 weeks without folate supplementation and to describe AG2034 pharmacokinetics.Methods: Adults with advanced malignancies were enrolled in cohorts of three per dose level with expansion to six upon observation of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was defined as the dose at which two of up to six patients experienced DLT. Upon identification of an MTD and evidence of cumulative toxicity, a lower intermediate dose was explored as a candidate phase II dose. AG2034 plasma concentrations were measured using an ELISA assay.Results and Conclusions: The recommended phase II dose is 5.0 mg/m2. DLTs were anemia, thrombocytopenia, mucositis, diarrhea, hyperbilirubinemia, fatigue, and insomnia. Toxicities were modestly cumulative over three courses. Pharmacokinetic analysis showed a dose-AUC0-24 relationship and a progressive increase in AG2034 AUC0-24 over three courses. Both pharmacokinetic and pharmacodynamic factors may contribute to the modest cumulative toxicity observed with AG2034. [ABSTRACT FROM AUTHOR]- Published
- 2000
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16. Hormone replacement after breast cancer.
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Spicer, D V and Pike, M C
- Subjects
- *
TAMOXIFEN , *OBESITY complications , *AGE distribution , *BREAST tumors , *HORMONES , *PROTEINS , *SURVIVAL , *THERAPEUTICS , *CHEMICAL inhibitors - Published
- 1993
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17. Tamoxifen and prevention.
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Ursin, G, Spicer, D V, and Pike, M C
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OSTEOPOROSIS prevention , *TAMOXIFEN - Published
- 1993
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18. Pilot Trial of a Gonadotropin Hormone Agonist with Replacement Hormones as a Prototype Contraceptive to Prevent Breast Cancer
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Spicer, D. V., Pike, M. C., Pike, A., and Rude, R.
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- 1993
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19. Reversal of gonadotropin-releasing hormone agonist induced reductions in mammographic densities on stopping treatment.
- Author
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Gram IT, Ursin G, Spicer DV, and Pike MC
- Subjects
- Adult, Breast Neoplasms diagnostic imaging, Estrogens, Conjugated (USP) therapeutic use, Female, Humans, Medroxyprogesterone Acetate therapeutic use, Premenopause, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms prevention & control, Estrogen Replacement Therapy, Gonadotropin-Releasing Hormone agonists, Leuprolide therapeutic use, Mammography
- Abstract
Previously, we described the reduction in mammographic densities that occurred in premenopausal women after 12 months on a hormonal regimen designed to be chemopreventive for breast (and ovarian) cancer consisting of a gonadotropin-releasing hormone agonist (GnRHA) plus low-dose add-back estrogen-progestin. We sought to determine whether the density reduction persisted with continuation of the regimen for 24 months, and, if so, whether the densities would return to baseline after the regimen was discontinued. Twenty-one women, 27-40 years of age, with a 5-fold greater than normal risk of breast cancer, were randomly assigned in a 2:1 ratio to the treatment group (14 women) and to a control group (7 women). The percentage of mammographic densities, calculated as the proportion of the breast area on the mammogram containing densities, were assessed blindly using a computer-based threshold method at baseline, after 12 and 24 months of treatment, and at between 6 and 12 months after treatment was stopped. The previously described percentage of mammographic density reductions of 9.7% (P = 0.012) after 12 months of treatment were increased slightly to 11.4% (P = 0.010) after 24 months of treatment, but the additional change was not statistically significant. Ten of 11 treated women assessed at 24 months had reduced percentages of mammographic densities compared with baseline. Six to 12 months after completion of treatment, the mean percentage of mammographic density in the treated group was no different from that at baseline (mean decline of 2.0%; P = 0.73). The women in the control group had no statistically significant changes in densities over the period of the study. Reductions in mammographic densities engendered by the GnRHA plus a low-dose add-back estrogen-progestin regimen persist as long as the women receive treatment. The densities return to baseline when the women resume normal menstrual cycles. These results confirm that mammographic densities are influenced by ovarian function. Improved efficacy of mammographic screening is to be expected as long as a woman continues on such a regimen. Whether such a regimen is chemopreventive for breast cancer remains to be established, but the recent report on a randomized trial of use of GnRHA alone in premenopausal breast cancer cases showing a marked reduction in incidence of contralateral disease provides strong support for the hypothesis.
- Published
- 2001
20. Mammographic density changes during the menstrual cycle.
- Author
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Ursin G, Parisky YR, Pike MC, and Spicer DV
- Subjects
- Adult, Breast Neoplasms prevention & control, Female, Humans, Middle Aged, Radiographic Image Enhancement, Reference Values, Sensitivity and Specificity, Breast physiology, Mammography methods, Menstrual Cycle physiology
- Abstract
The ability to detect small tumors is impaired in dense mammograms. It has been suggested that the sensitivity of mammograms could be lower in mammograms obtained during the luteal phase of the menstrual cycle. We examined the change in mammographic density from the follicular to the luteal phase of the menstrual cycle in 11 women. Although the average increase in densities was quite small (1.2%; P = 0.08), six women had clinically significant increases (1.4-7.8%), suggesting that premenopausal women should undergo mammographic examinations in the follicular part of the menstrual cycle.
- Published
- 2001
21. Future possibilities in the prevention of breast cancer: luteinizing hormone-releasing hormone agonists.
- Author
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Spicer DV and Pike MC
- Subjects
- Breast drug effects, Breast Neoplasms epidemiology, Breast Neoplasms therapy, Clinical Trials as Topic, Endometrium drug effects, Epithelial Cells drug effects, Estrogen Replacement Therapy, Estrogens metabolism, Feasibility Studies, Female, Forecasting, Goserelin adverse effects, Goserelin pharmacology, Goserelin therapeutic use, Humans, Incidence, Mammography, Methyltestosterone therapeutic use, Multicenter Studies as Topic, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary prevention & control, Osteoporosis chemically induced, Ovariectomy, Ovary drug effects, Ovary metabolism, Pilot Projects, Premenopause, Progesterone metabolism, Progestins administration & dosage, Progestins therapeutic use, Risk, Secretory Rate drug effects, Breast Neoplasms prevention & control, Gonadotropin-Releasing Hormone agonists
- Abstract
The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities.
- Published
- 2000
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22. Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation.
- Author
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Roberts JD, Poplin EA, Tombes MB, Kyle B, Spicer DV, Grant S, Synold T, and Moran R
- Subjects
- Administration, Oral, Adult, Aged, Anemia prevention & control, Drug Administration Schedule, Drug Evaluation, Erythrocyte Count, Female, Folic Acid pharmacology, Folic Acid Antagonists pharmacokinetics, Hematinics pharmacology, Humans, Infusions, Intravenous, Lymphoma metabolism, Male, Middle Aged, Neoplasms metabolism, Tetrahydrofolates pharmacokinetics, Anemia chemically induced, Folic Acid administration & dosage, Folic Acid Antagonists adverse effects, Hematinics administration & dosage, Lymphoma drug therapy, Neoplasms drug therapy, Tetrahydrofolates adverse effects
- Abstract
Purpose: Lometrexol [(6R)-5,10-dideaza-5,6,7,8-tetrahydrofolate] is the prototype folate antimetabolite that targets the de novo purine synthesis pathway. Early phase I trials were confounded by cumulative myelosuppression that prevented repetitive administration. Subsequent preclinical and clinical studies suggested that coadministration of folic acid might favorably modulate lometrexol toxicity without eliminating potential antitumor activity. We set out to determine if concurrent folic acid would allow administration of lometrexol on a weekly schedule, and, if so, to identify an appropriate dose combination for phase II trials. Pharmacokinetic and metabolism studies were undertaken in an attempt to improve our understanding of lometrexol pharmacodynamics., Methods: Patients with advanced cancer received daily oral folic acid beginning 7 days before lometrexol and continuing for 7 days beyond the last lometrexol dose. Lometrexol was administered by short i.v. infusion weekly for 8 weeks. Scheduled lometrexol doses were omitted for toxicity of more than grade 2 present on the day of treatment, and dose-limiting toxicity was prospectively defined in terms of frequency of dose omission as well as the occurrence of severe toxic events. Plasma and whole blood total lometrexol contents (lometrexol plus lometrexol polyglutamates) were measured in samples taken just prior to each lometrexol dose., Results: A total of 18 patients were treated at five lometrexol dose levels. The maximum tolerated dose was identified by frequent dose omission due to thrombocytopenia and mucositis. The recommended phase II dose combination is lometrexol 10.4 mg/m(2) per week i.v. with folic acid 3 mg/m(2) per day orally. One patient with melanoma experienced a partial response, and three patients, two with melanoma and one with renal cell carcinoma, experienced stable disease. Lometrexol was not detectable in any predose plasma sample tested. The total red blood cell content of lometrexol increased over several weeks and then appeared to plateau., Conclusions: Weekly administration of lometrexol is feasible and well-tolerated when coadministered with daily oral folic acid. The nature of the interaction between natural folates and lometrexol that renders this schedule feasible remains unclear. A definition of dose-limiting toxicity that incorporated attention to dose omissions allowed efficient identification of a recommended phase II dose that reflects the maximum feasible dose intensity for a weekly schedule. Lometrexol is a promising, anticancer agent.
- Published
- 2000
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23. The detection of changes in mammographic densities.
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Ursin G, Astrahan MA, Salane M, Parisky YR, Pearce JG, Daniels JR, Pike MC, and Spicer DV
- Subjects
- Adult, Breast Neoplasms prevention & control, Female, Humans, Image Processing, Computer-Assisted, Neoplasms, Hormone-Dependent prevention & control, Breast Neoplasms diagnostic imaging, Contraceptives, Oral, Hormonal therapeutic use, Gonadotropin-Releasing Hormone agonists, Mammography, Neoplasms, Hormone-Dependent diagnostic imaging
- Abstract
We previously reported reductions in mammographic densities in women participating in a trial of a gonadotropin-releasing hormone agonist (GnRHA)-based regimen for breast cancer prevention. In our previous report, we compared (by simultaneous evaluation) three basic elements of mammographic densities. The purpose of the present study was to evaluate whether a standard (expert) method of measuring mammographic densities would detect such changes in densities and whether a novel nonexpert computer-based threshold method could do so. Mammograms were obtained from 19 women at baseline and 12 months after randomization to the GnRHA-based regimen. The extent of mammographic densities was determined by: (a) a standard expert outlining method developed by Wolfe and his colleagues (Am. J. Roentgenol., 148: 1087-1092, 1987); and (b) a new computer-based threshold method of determining densities. The results from both the expert outlining method and the computer-based threshold method were highly consistent with the results of our original (simultaneous evaluation) method. All three methods yielded statistically significant reductions in densities from baseline to the 12-month follow-up mammogram in women on the contraceptive regimen. The difference between the treated and the control group was statistically significant with the expert outlining method and was of borderline statistical significance with the computer-based threshold method. The computer-based results correlated highly (r > 0.85) with the results from the expert outlining method. Both the standard expert outlining method and the computer-based threshold method detected the reductions we had previously noted in mammographic densities induced by the GnRHA-based regimen.
- Published
- 1998
24. Progesterone concentrations--physiologic or pharmacologic?
- Author
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Spicer DV, Ursin G, and Pike MC
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- Administration, Topical, Breast drug effects, Breast metabolism, Estradiol administration & dosage, Estradiol metabolism, Female, Humans, Luteal Phase, Progesterone administration & dosage, Progesterone metabolism
- Published
- 1996
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25. Can mammographic densities predict effects of tamoxifen on the breast?
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Ursin G, Pike MC, Spicer DV, Porrath SA, and Reitherman RW
- Subjects
- Adult, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms diagnostic imaging, Breast Neoplasms prevention & control, Estrogen Antagonists therapeutic use, Mammography, Tamoxifen therapeutic use
- Published
- 1996
- Full Text
- View/download PDF
26. Oral vinorelbine (Navelbine) in the treatment of advanced breast cancer.
- Author
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Winer EP, Chu L, and Spicer DV
- Subjects
- Administration, Oral, Aged, Aged, 80 and over, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Clinical Trials, Phase II as Topic, Female, Humans, Vinblastine administration & dosage, Vinblastine pharmacokinetics, Vinblastine therapeutic use, Vinorelbine, Antineoplastic Agents administration & dosage, Breast Neoplasms drug therapy, Vinblastine analogs & derivatives
- Abstract
Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) has been formulated as a liquid-filled, soft gelatin capsule. Pharmacokinetic studies of this agent indicate that it has a large volume of distribution, a long terminal half-life, and a high clearance rate. The pharmacokinetics of vinorelbine are similar whether the drug is administered orally or intravenously. Oral vinorelbine has a low bioavailability, which may be due to a high first-pass effect. Preliminary results from two multicenter phase II trials of oral vinorelbine in patients with advanced breast cancer are presented. In one study of 98 advanced breast cancer patients aged 65 years and older with limited prior therapy, the response rate of oral vinorelbine was 24% (complete response, 5%; partial response, 19%). In a study of 131 heavily pretreated patients with advanced breast cancer, the response rate of oral vinorelbine was 11% (complete response, 0%; partial response, 11%). In both studies, oral vinorelbine was generally well tolerated. As with intravenous administration, neutropenia is common and neuropathy is infrequent. In contrast to intravenous administration, nausea, vomiting, and diarrhea are common. Based on these preliminary results, further clinical investigation of oral vinorelbine is warranted.
- Published
- 1995
27. The endocrine prevention of breast cancer.
- Author
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Spicer DV, Krecker EA, and Pike MC
- Subjects
- Cell Division, Female, Gonadal Steroid Hormones physiology, Growth Substances physiology, Humans, Breast Neoplasms prevention & control, Estrogen Antagonists therapeutic use, Progestins antagonists & inhibitors
- Abstract
A clear explanation for the high incidence of breast cancer in modern women is now possible. The risk of breast cancer rises steeply from menarche until menopause. Associated with the reproductive process, the ovary, including the corpus luteum, produces substantial amounts of estrogen and progesterone, both of which induce growth of the breast epithelium. This sex-steroid-driven breast epithelial cell proliferation increases the risk of carcinogenesis by accelerating the occurrence of somatic genetic errors. Postmenopausally, as there is little cell proliferation, the breast epithelium is more "resistant" to mutagenic effects, and breast cancer risk rises at a low rate. Unfortunately, the genetic errors accumulated during the premenopausal period are not lost following menopause, and breast cancer risk remains high. Sex-steroid antagonists, such as tamoxifen, may reduce breast cancer incidence both by blocking breast epithelial cell proliferation and by direct antitumor effects on clinically occult breast cancers. The rationale for a contraceptive designed to reduce breast cell proliferation by decreasing premenopausal sex-steroid exposure is presented.
- Published
- 1995
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28. Phase II clinical trial of carboplatin, ifosfamide, with oral mesna for metastatic breast carcinoma.
- Author
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Turrill M, Spicer DV, Kelley AS, Herman RL, Russell CA, and Muggia FM
- Subjects
- Adult, Ambulatory Care, Carboplatin administration & dosage, Cystitis chemically induced, Cystitis prevention & control, Female, Humans, Ifosfamide administration & dosage, Ifosfamide adverse effects, Mesna administration & dosage, Middle Aged, Remission Induction, Adenocarcinoma drug therapy, Adenocarcinoma secondary, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Twenty-five women with advanced breast carcinoma refractory to first-line chemotherapy entered a phase II trial to evaluate the efficacy of ifosfamide and carboplatin. Additionally the trial assessed the clinical usefulness of oral 2-mercaptoethane sulfonate (mesna) for urothelial protection. Two partial remissions were observed (8%); toxicity was significant but acceptable, with no treatment-related deaths. The combination of ifosfamide and carboplatin had little activity as the second-line treatment in our population of patients with heavily pretreated metastatic breast cancer. Oral mesna was effective for urothelial protection, permitting outpatient administration of ifosfamide.
- Published
- 1995
- Full Text
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29. Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk.
- Author
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Spicer DV, Ursin G, Parisky YR, Pearce JG, Shoupe D, Pike A, and Pike MC
- Subjects
- Adult, Breast Neoplasms diagnostic imaging, Contraceptives, Oral, Hormonal administration & dosage, Delayed-Action Preparations, Female, Humans, Leuprolide administration & dosage, Risk, Breast Neoplasms prevention & control, Contraceptives, Oral, Hormonal therapeutic use, Leuprolide therapeutic use, Mammography
- Abstract
Background: It has been known for some time that oral contraceptives substantially reduce the risk of endometrial and ovarian cancer, but they do not reduce the risk of breast cancer. A hormonal contraceptive regimen has been developed which uses a gonadotropin-releasing hormone against (GnRHA) to suppress ovarian function, and this regimen includes the administration of very low doses of both estrogen and progestogen. This hormonal contraceptive regimen attempts to minimize exposure of the breast epithelium to these steroids and to preserve the maximum beneficial effects of estrogen, while still preventing endometrial hyperplasia., Purpose: Our purpose was to determine whether changes occurred in mammographic densities between baseline and 1 year for women on this hormonal contraceptive regimen with reduced estrogen and progestogen levels compared with women in a control group., Methods: Twenty-one women were randomly assigned in a 2:1 ratio to the GnRHA-based contraceptive group (14 women) or to a control group (seven women). The contraceptive group received the following: 7.5 mg leuprolide acetate depot by intramuscular injection every 28 days; 0.625 mg conjugated estrogen by mouth for 6 days out of 7 every week; and 10 mg medroxyprogesterone acetate orally for 13 days every fourth 28-day cycle. The control group received no medication. Baseline and 1-year follow-up mammograms of contraceptive and control subjects were reviewed in a blinded fashion by two radiologists., Results: Comparison of the changes between the baseline and 1-year mammograms in the two groups of women showed significant (P = .039) reduction in mammographic densities at 1 year for women on the contraceptive regimen. Assessing the reduction in mammographic densities by noting the fineness of fibrous septae showed a highly significant (P = .0048) difference in the contraceptive regimen group. One of the women on the contraceptive regimen was withdrawn from the study because of poor compliance., Conclusion: The reduced estrogen and progestogen exposures to the breast that were achieved by the hormonal contraceptive regimen resulted in substantial reductions in follow-up mammographic densities at 1 year compared with baseline. Although there is no direct evidence that such a reduction in densities will lead to a reduced risk of breast cancer, indirect evidence for a protective effect of this regimen is that early menopause reduces breast cancer risk, and that menopause is associated with a reduction in mammographic densities.
- Published
- 1994
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- View/download PDF
30. Sex steroids and breast cancer prevention.
- Author
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Spicer DV and Pike MC
- Subjects
- Adult, Age Factors, Bone Density drug effects, Breast Neoplasms chemically induced, Breast Neoplasms epidemiology, Cardiovascular Diseases prevention & control, Case-Control Studies, Cell Division drug effects, Contraceptives, Oral, Combined adverse effects, Contraceptives, Oral, Hormonal adverse effects, Drug Utilization, Endometrial Neoplasms chemically induced, Endometrial Neoplasms epidemiology, Endometrial Neoplasms prevention & control, Endometrium drug effects, Endometrium pathology, Estrogen Replacement Therapy adverse effects, Female, Humans, Hyperplasia, Incidence, Leuprolide pharmacology, Leuprolide therapeutic use, Middle Aged, Osteoporosis chemically induced, Ovarian Neoplasms epidemiology, Ovarian Neoplasms prevention & control, Pilot Projects, Premenopause, Progestins administration & dosage, Progestins adverse effects, Reproductive History, Risk Factors, Breast Neoplasms prevention & control, Contraceptives, Oral, Combined therapeutic use, Contraceptives, Oral, Hormonal therapeutic use, Estrogens, Gonadotropin-Releasing Hormone agonists, Neoplasms, Hormone-Dependent prevention & control, Progesterone, Progestins therapeutic use, Testosterone therapeutic use
- Abstract
Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1994
31. Contraception and cancer prevention.
- Author
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Ursin G, Spicer DV, and Pike MC
- Subjects
- Americas, Biology, California, Contraceptive Agents, Contraceptive Agents, Female, Developed Countries, Disease, Endocrine System, Family Planning Services, Hormones, Neoplasms, North America, Physiology, United States, Breast Neoplasms, Case-Control Studies, Cell Biology, Contraception, Endometrial Neoplasms, Estrogens, Lipids, Medroxyprogesterone Acetate, Ovarian Neoplasms, Pilot Projects, Pituitary Hormone-Releasing Hormones
- Published
- 1994
32. Breast cancer prevention through modulation of endogenous hormones.
- Author
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Spicer DV and Pike MC
- Subjects
- Adult, Aged, Cell Division drug effects, Female, Gonadal Steroid Hormones pharmacology, Humans, Middle Aged, Risk Factors, Breast Neoplasms prevention & control, Contraceptives, Oral, Combined therapeutic use, Gonadal Steroid Hormones physiology
- Abstract
The use of exogenous sex-steroids for hormonal contraception is important to the way of life of many modern women. The widespread use of hormonal contraceptives represents a unique opportunity to have a substantial positive impact on women's health. The observation that users of oral combination type contraceptives have a reduced risk of ovarian cancer should encourage the extension of contraceptive development to address the most important malignancy facing modern women, breast cancer. Epidemiological evidence strongly suggests that both estrogens and progestogens contribute to breast cancer risk, and account for the steep rise in risk seen during the premenopausal years. Studies of normal breast epithelial cell proliferation confirm that progestogens are breast mitogens, and explain why current contraceptives, which are progestogen dominant, do not prevent breast cancer. A long-acting depot contraceptive can be developed which releases: 1) an agonist of gonadotropin releasing hormone to suppress ovarian function; and 2) sex-steroids at doses below those in current contraceptives, and below those associated with ovulation. Such a contraceptive should provide substantial life-time protection against both breast and ovarian cancer, and would retain many of the other health benefits of current contraceptives.
- Published
- 1993
- Full Text
- View/download PDF
33. Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk.
- Author
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Pike MC, Spicer DV, Dahmoush L, and Press MF
- Subjects
- Breast Neoplasms etiology, Cell Division, Female, Humans, Menopause physiology, Pregnancy physiology, Risk Factors, Breast pathology, Breast Neoplasms epidemiology, Estrogens physiology, Progestins physiology
- Published
- 1993
- Full Text
- View/download PDF
34. The chemoprevention of breast cancer by reducing sex steroid exposure: perspectives from epidemiology.
- Author
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Pike MC and Spicer DV
- Subjects
- Breast Neoplasms epidemiology, Breast Neoplasms etiology, Cell Division, Contraceptives, Oral therapeutic use, Estrogens physiology, Estrogens therapeutic use, Female, Humans, Middle Aged, Pregnancy, Progesterone physiology, Progesterone therapeutic use, Risk Factors, Breast Neoplasms prevention & control, Contraceptives, Oral adverse effects, Estrogens adverse effects, Progesterone adverse effects
- Abstract
Mitogenesis is a major driving force in neoplastic development. Blocking the effect of breast cell mitogens by reducing the actual exposure of the breast to these mitogens is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. A woman's exposure to ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the synthetic estrogen and progestogen in the COCs effectively replace ovarian estrogens and progesterone, so that breast cell exposure to these hormones is not decreased. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist (GnRHA) to suppress ovarian function and compensate for the resulting hypoestrogenemia with low-dose hormone replacement therapy. Compared to modern COCs, estrogen exposure can be reduced by approximately 60%, and progestogen dose by more than 80%. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years. The possibility that a practical contraceptive could achieve such a major benefit is shown by the dramatic decline in the incidence of both ovarian and endometrial cancer in young women in the U.S. over the last 3 decades--a direct result of COC use.
- Published
- 1993
- Full Text
- View/download PDF
35. The prevention of breast cancer through reduced ovarian steroid exposure.
- Author
-
Spicer DV and Pike MC
- Subjects
- Breast Neoplasms blood, Breast Neoplasms epidemiology, Breast Neoplasms etiology, Cell Division, Endometrial Neoplasms blood, Endometrial Neoplasms prevention & control, Estradiol blood, Female, Humans, Incidence, Menopause blood, Menstrual Cycle blood, Ovarian Neoplasms blood, Ovarian Neoplasms etiology, Progesterone blood, Breast Neoplasms prevention & control, Contraceptives, Oral, Combined administration & dosage, Endometrial Neoplasms etiology, Estrogen Replacement Therapy, Ovarian Neoplasms prevention & control
- Abstract
Analysis of epidemiologic data on cancers of the breast, ovary and endometrium; the effects of endogenous hormones on cell proliferation; and current carcinogenesis concepts, suggest that hormonal contraceptives can be developed that will reduce lifetime risk of all 3 cancers. The 'unopposed-estrogen hypothesis' accounts for endometrial cancer risk factors. Ovarian cancer risk is closely related to the total frequency of ovulation. The risk of breast cancer can be explained by an 'estrogen-plus-progestogen hypothesis'. On the basis of this analysis an hormonal contraceptive regimen has been developed consisting of a gonadotropin-releasing hormone agonist (GnRHA) plus continuous low-dose add-back estrogen and a short course of progestogen every fourth month. The total dose of add-back estrogen is estimated to be approximately 38% that in present-day low-dose combination-type oral contraceptives (COCs). The total dose of progestogen is approximately 15% that in COCs. This regimen prevents ovulation and should thus reduce ovarian cancer risk. It also reduces the exposure of the endometrium to unopposed estrogen, and the exposure of the breast to estrogen-plus-progestogen. It is estimated that use of such a regimen for 10 years will only reduce lifetime risk of endometrial cancer by one-sixth, but lifetime risk of ovarian cancer is estimated to be reduced by two-thirds, and lifetime risk of breast cancer is estimated to be reduced by one-half.
- Published
- 1992
- Full Text
- View/download PDF
36. Low-dose recombinant interleukin-2 and low-dose cyclophosphamide in metastatic breast cancer.
- Author
-
Spicer DV, Kelley A, Herman R, Dean G, Stevenson L, and Mitchell MS
- Subjects
- Adult, Breast Neoplasms drug therapy, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Evaluation, Female, Humans, Middle Aged, Recombinant Proteins therapeutic use, T-Lymphocytes, Regulatory drug effects, Breast Neoplasms secondary, Breast Neoplasms therapy, Cyclophosphamide therapeutic use, Immunotherapy, Interleukin-2 therapeutic use
- Abstract
We undertook a preliminary study to examine the response rate of recombinant interleukin-2 (rIL-2) in patients with advanced measurable breast cancer, in a phase II clinical trial. The regimen we utilized was designed to allow outpatient administration. A treatment cycle consisted of low-dose cyclophosphamide (350 mg/m2) given on day -3 followed by the bolus administration of rIL-2 (3.6 x 10(6) Cetus units/m2) on days 1-5, and 8-12. Toxicity was significant but acceptable. One partial remission was seen in 13 evaluable patients. In 2 additional patients clear evidence of an antitumor response was observed. The study was terminated prematurely owing to a shortage of rIL-2. Additional evaluation of rIL-2 in breast cancer appears warranted.
- Published
- 1992
- Full Text
- View/download PDF
37. GnRH agonists as contraceptive agents: predicted significantly reduced risk of breast cancer.
- Author
-
Spicer DV, Shoupe D, and Pike MC
- Subjects
- Bone and Bones metabolism, Breast Neoplasms epidemiology, Contraceptive Agents, Female adverse effects, Contraceptive Agents, Female pharmacology, Endometrial Neoplasms epidemiology, Endometrial Neoplasms prevention & control, Estrogens, Conjugated (USP) pharmacology, Female, Gonadotropin-Releasing Hormone adverse effects, Gonadotropin-Releasing Hormone pharmacology, Humans, Leuprolide pharmacology, Lipid Metabolism, Liver metabolism, Medroxyprogesterone analogs & derivatives, Medroxyprogesterone pharmacology, Medroxyprogesterone Acetate, Ovarian Neoplasms epidemiology, Ovarian Neoplasms prevention & control, Ovary drug effects, Risk Factors, Breast Neoplasms prevention & control, Gonadotropin-Releasing Hormone antagonists & inhibitors
- Abstract
Gonadotrophin-releasing hormone agonists (GnRHAs) were investigated as contraceptive agents from the late 1970's to the mid-1980's. They were abandoned as they appeared to offer no advantage over conventional combination-type oral contraceptives (COCs). This conclusion appears to be incorrect. We propose here a contraceptive regimen of a depot formulation of a GnRHA plus add-back estrogen and intermittent progestogen. The dose of add-back sex-steroids is substantially less than that in COCs; this reduction in sex-steroids should lead to a major reduction in lifetime breast cancer occurrence.
- Published
- 1991
- Full Text
- View/download PDF
38. Ovarian cancer and long-term tamoxifen in premenopausal women.
- Author
-
Spicer DV, Pike MC, and Henderson BE
- Subjects
- Breast Neoplasms prevention & control, Female, Humans, Risk Factors, Menopause, Ovarian Neoplasms chemically induced, Ovulation Induction methods, Tamoxifen adverse effects
- Published
- 1991
- Full Text
- View/download PDF
39. Tolerance of extended (28 day) continuous infusion of 5-fluorouracil in advanced head and neck cancer.
- Author
-
Grunberg SM, Clay C, and Spicer DV
- Subjects
- Adult, Aged, Drug Eruptions etiology, Drug Tolerance, Female, Fluorouracil administration & dosage, Fluorouracil therapeutic use, Head and Neck Neoplasms pathology, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasm Metastasis, Stomatitis chemically induced, Fluorouracil adverse effects, Head and Neck Neoplasms drug therapy
- Abstract
Since continuous exposure increases the cytotoxicity of 5-Fluorouracil, this agent is now commonly administered by 4-5 day continuous infusions. However Phase I studies have suggested that infusion of doses up to 450 mg/m2/day for at least 28 days may be possible. In the present study 12 patients with advanced head and neck cancer were treated with continuous infusion 5-Fluorouracil at starting doses of 400-450 mg/m2/day for 28 days followed by a 14 day rest period. Patients received a median of 2.5 cycles over 10 weeks for a median total 5-Fluorouracil dose of 12,700 mg/m2. One patient achieved Partial Response. Significant stomatitis (Grade II or greater) was seen more frequently than predicted from Phase I studies (8/12 patients) and was the most common cause for dose reduction. Diarrhea, emesis, palmar/plantar syndrome and skin rash were also noted. No significant myelosuppression was seen. Extremely large amounts of 5-Fluorouracil can be delivered to head and neck cancer patients by extended infusion. However due to the high frequency of stomatitis in this population, lower starting doses than those used in this study may be required.
- Published
- 1991
- Full Text
- View/download PDF
40. Tamoxifen and estrogen replacement therapy as agents of disease prevention.
- Author
-
Spicer DV, Pike MC, Henderson BE, and Groshen S
- Subjects
- Coronary Disease mortality, Drug Administration Schedule, Female, Humans, Tamoxifen administration & dosage, Coronary Disease prevention & control, Estrogen Replacement Therapy, Tamoxifen therapeutic use
- Published
- 1991
- Full Text
- View/download PDF
41. Reevaluation of the maximum tolerated dose of continuous venous infusion of 5-fluorouracil with pharmacokinetics.
- Author
-
Spicer DV, Ardalan B, Daniels JR, Silberman H, and Johnson K
- Subjects
- Diarrhea chemically induced, Fluorouracil pharmacokinetics, Fluorouracil toxicity, Humans, Infusions, Intravenous, Skin drug effects, Fluorouracil administration & dosage
- Abstract
5-Fluorouracil (5-FU) was administered as a continuous ambulatory venous infusion to 25 patients in a Phase I trial. The principal dose limiting toxic effect observed was mucositis. Skin rash and diarrhea occurred less frequently. Hematological toxicity was modest, and no hepatic toxicity was seen. One partial remission of 138 days duration was seen in a patient with metastatic breast carcinoma who was previously refractory to a 5-FU combination regimen. Patient tolerance of 5-FU delivered in this manner appeared highly variable. On the basis of this trial, we recommend that future studies evaluating the efficacy of long-term venous infusion of 5-FU should utilize a dosage of 450 mg/m2/day.
- Published
- 1988
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