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Biomedical subjects

J N Ingle

Publications and source records attributed to J N Ingle.

At least 109 records · Page 6Linked to original sources
PubMed1984

Additive hormonal therapy in women with advanced breast cancer.

A great deal of work has been done over the last decade in the assessment of additive hormonal treatment approaches in women with advanced breast cancer. This work has been prompted by a number of factors which include: (1) the introduction of new hormonal agents, (2) increased knowledge of the physiologic actions of several hormonal agents, (3) the development of hormonal receptor assays to better predict the probability of hormonal responsiveness in a given patient, and (4) the apparent plateau in efficacy of cytotoxic chemotherapeutic approaches. The hormonal agents that have been studied most extensively in the recent past include tamoxifen (an antiestrogen), aminoglutethimide (an aromatase inhibitor), and medroxyprogesterone acetate (a progestin). In postmenopausal women, several agents exist that appear about equal in efficacy; but, currently, tamoxifen appears to be preferred as the initial hormonal treatment, primarily because of its low incidence of side effects. Studies involving combination hormonal therapy have produced interesting results, but further work is needed to establish superiority over tamoxifen alone. In premenopausal women, tamoxifen does have antitumor activity in some patients but has not been established as a replacement for oophorectomy. Properly conducted comparative trials will remain essential for the determination of the proper place of newer hormonal therapy approaches in clinical practice.

Aminoglutethimide↗
PubMed1984

Integration of hormonal agents and chemotherapy for the treatment of women with advanced breast cancer.

Efforts have been made to improve the efficacy of combination chemotherapeutic regimens for advanced breast cancer by integrating additive hormonal agents. Results with respect to the value of such an approach are conflicting, and the routine use of chemohormonal therapy in clinical practice has not been established. Further work in this area is needed, especially in regard to the use of hormonal agents as manipulators of tumor cell kinetics to enhance the effectiveness of chemotherapy. In addition, clinical trials have compared the results of hormonal therapy alone with those of chemohormonal therapy; currently, the use of hormonal agents alone seems to be preferable for the initial treatment of most postmenopausal women with advanced breast cancer. The exception to this practice would be in those patients who are clinically not candidates for hormonal therapy because of the site, extent, or tempo of disease or because of the absence of hormonal receptors.

Androgens↗
PubMed1984

A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.

We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Cis-diamminedichloroplatinum (II) administered by 24-hour infusion in the treatment of patients with advanced upper aerodigestive cancer.

A regression rate of 12% (4/33) among patients with advanced upper aerodigestive carcinomas who received an intravenous regimen of cis-diamminedichloroplatinum, 90 mg/m2/24 hours each three weeks was achieved. The response rate was 13% (3/23) among patients with typical squamous cell carcinoma. Most individuals had received extensive prior surgery and/or radiation therapy. Nineteen patients had ECOG performance score 0, 1. A median time to progression and survival of 1.6 months and 6.7 months, respectively, were associated with moderate to severe nausea and vomiting in virtually all patients. These results differ from previous reports of single agent platinum regimens which have achieved regression rates of approximately 40% among apparently comparable patients. Subtle clinically inapparent differences between study populations and the influence of yet unrecognized covariates may have impacted on the response discrepancy. Innovative studies of the high-dose, infusion platinum therapy may clarify the efficacy of the program in patients with advanced head and neck cancer.

Carcinoma↗
PubMed1983

Cyclophosphamide, doxorubicin, and cisplatin combined in the treatment of advanced sarcomas.

Twenty-five patients with evaluable histologically confirmed inoperable metastatic sarcomas were treated once every four weeks with cyclophosphamide, doxorubicin, and cisplatin in doses of 400, 40, and 60 mg/m2, respectively. Cyclophosphamide and doxorubicin were given by rapid intravenous injection followed immediately by cisplatin by slow intravenous infusion (2-6 hr) in 1 liter of 0.45% saline with mannitol added. Leukopenia, alopecia, and vomiting were common side effects and three patients refused further treatment because of vomiting following their initial courses. No drug-related deaths occurred and we removed no one from the study because of toxicity problems. Among the 9 patients who experienced objective tumor regression were 2 of 2 with hemangiosarcoma, 3 of 5 with malignant fibrous histiocytoma, 3 of 5 with osteosarcoma, and 1 of 1 with pleomorphic liposarcoma of bone. Although not therapeutically gratifying, these results appear to be better than any previously observed at our institution.

Adolescent↗
PubMed1982

Phase II study of high-dose tamoxifen (NSC-180973) in patients with disseminated malignant melanoma.

Seventeen patients with disseminated malignant melanoma received a daily oral regimen of tamoxifen, 100 mg/m2. All patients had prior chemotherapy and predominantly visceral involvement. None of the patients had an objective regression and most (71%) had progressive disease at the time of first reassessment. Moderate to severe nausea occurred in 24% of patients. In the dose and schedule used in this study, tamoxifen is ineffective in patients with advanced malignant melanoma and prior chemotherapy exposure.

Drug Administration Schedule↗
PubMed1982

Randomized clinical trial of megestrol acetate versus tamoxifen in paramenopausal or castrated women with advanced breast cancer.

Fifty-five women with progressive metastatic breast cancer who were paramenopausal (1 to less than 5 years since last menstrual period) or castrated were randomized to receive either megestrol acetate (150 mg/m2 daily in three divided doses) or tamoxifen (10 mg twice daily). The regression rate (complete plus partial) was higher for tamoxifen (26%) than for megestrol acetate (14%), but not significantly so. Analysis of time to treatment failure showed no significant difference (medians: megestrol acetate, 65 days; tamoxifen, 58 days). There was survival advantage associated with megestrol acetate (P = 0.02 after adjustment for stratification factors) that is difficult to interpret given the results of analysis of regression and time to treatment failure for the two agents.

Adult↗
PubMed1982

An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advances breast cancer undergoing oophorectomy: a later analysis.

In 1977 we reported our results of an ongoing randomized clinical trial evaluating early or delayed adjuvant chemotherapy utilizing 5-flourouracil, cytoxan and prednisone in premenopausal patients with recurrent or advanced breast cancer. At that time the group receiving early systemic chemotherapy was shown to have an improved progression-free interval and appeared to have a trend toward improved survival. The results of subsequent analysis after over 4 more years of follow-up indicate however, that while early employment of systemic chemotherapy does indeed prolong the progression-free interval, and while this advantage has been maintained, there is no survival advantage shown for either group of patients.

Adult↗
PubMed1982

A preliminary assessment of factors associated with recurrent disease in a surgical adjuvant clinical trial for patients with breast cancer with special emphasis on the aggressiveness of therapy.

Two hundred ninety-three patients were randomly assigned to three treatment regimens following mastectomy for operable but prognostically unfavorable breast cancer: L-PAM, CFP, or CFP with radiation therapy. For premenopausal patients an increased risk of recurrence was associated with the presence of unfavorable local signs, large number of lymph nodes involved, greater body weight, younger age, and L-PAM treatment. For the postmenopausal patients only three factors were associated with an increased risk of recurrent disease: large tumor size, large number of lymph nodes involved, and inner/central location of the primary lesion. Specifically, the treatment employed has shown no effect. Of particular importance is the fact that for neither group of patients does our experience presently demonstrate clear association of recurrent disease with the level of drug dose administered. Furthermore, evidence suggests that although patients who experience little or no myelosuppression have significantly worse disease-free intervals than patients who experience moderate or severe myelosuppression, here is no benefit for severe myelosuppression over moderate, myelosuppression.

Adult↗
PubMed1982

Progress report on two clinical trials in women with advanced breast cancer. Trial I: tamoxifen versus tamoxifen plus aminoglutethimide. Trial II: aminoglutethimide in patients with prior tamoxifen exposure.

A progress report is presented on two on-going clinical trials in women with advanced breast cancer. In Trial I to date, 56 patients have been randomized to tamoxifen (TAM) alone or TAM plus aminoglutethimide (AG) (plus hydrocortisone). Patients failing TAM can then receive AG. The two groups are reasonably well balanced with respect to prior hormonal therapy exposure (TAM, 19%; TAM plus AG, 17%), age, disease-free interval, performance score, and estrogen receptor status. The TAM plus AG group has a higher incidence of visceral dominant disease (41 versus 26%) and prior chemotherapy exposure (41 versus 33%). Responses have been observed in 7 of 27 (26%) patients on TAM and 11 of 28 (39%) on TAM plus AG. Median times to treatment failure (defined as disease progression, unacceptable toxicity, or patient refusal) are 211 and 123 days, respectively (log-rank on time to treatment failure, p = 0.87). Toxicity is greater for TAM plus AG with a higher incidence of skin rash, lethargy, and dizziness. Thrombotic events were seen in one patient on TAM and two patients on TAM plus AG. One patient on TAM plus AG developed leukopenia and sepsis. The data are too preliminary for one to draw firm conclusions regarding relative efficacy. In TRial II to date, 35 patients with prior tamoxifen exposure have received AG. The mean number of prior systemic therapies is 3.2 (range, 1 to 7). The response rate is 20% and similar with (21%) or without (19%) prior chemotherapy exposure. The median time to treatment failure is 92 days. One patient developed leukopenia and sepsis. Additional patient accrual is necessary to allow characterization of potential efficacy within prognostically important subsets.

Adult↗
PubMed1981

Chemotherapy for advanced head and neck cancer with the combination adriamycin, cyclophosphamide, and cis-diamminedichloroplatinum (II): preliminary assessment of a one-day vs. three-day drug regimen.

Fourteen patients with advanced head and neck carcinomas received a monthly intravenous regimen of Adriamycin, 40 mg/m2, day 1; cyclophosphamide, 400 mg/m2, day 3; and cis-diamminedichloroplatinum, 20 mg/m2/1 hour, days 1-3 (CAP-3). A regression rate of only 7% (0/12 squamous cell carcinomas; 1/2 adenocarcinomas) and a median survival of five months for all patients was accompanied by considerable gastrointestinal toxicity. These results strikingly diverge from a prior study that achieved a 64% (16/25) regression rate using comparable doses of each agent but was administered by rapid infusion on one day each month (CAP-1). Admittedly, the relatively impaired performance scores of the CAP-3 participants may have had some impact on these discouraging results. On the other hand, the maximum therapeutic efficacy of the combination Adriamycin, cyclophosphamide, and cis-platinum may well depend upon subtle interactions of cell cycle kinetics and dosage and schedule of each agent.

Adenocarcinoma↗
PubMed1981

Malignant, predominantly lymphocytic thymoma with central and peripheral nervous system metastases.

Histologic features of an invasive mediastinal tumor found in a 25-year-old woman fulfilled the accepted criteria for diagnosis of predominantly lymphocytic thymoma. Histochemical and cell marker studies indicated that the neoplasm contained a preponderance of T lymphocytes. After surgical debulking of the mass, aggressive radiotherapy and chemotherapy eradicated all evidence of thoracic disease. However, six months after the initial diagnosis, rapid development of cranial nerve and brainstem metastases--without detectable recurrent disease elsewhere--resulted in the patient's death. Autopsy examination revealed the presence of peripheral nerve metastases as well. A review of the literature disclosed fewer than 10 cases of central nervous system metastasis from thymoma. In only two of these were there clinicopathologic features similar to those seen in this case.

Adult↗
PubMed1981

Cyclophosphamide, adriamycin, and cis-diamminedichloroplatinum (II) in the treatment of patients with advanced head and neck cancer.

Twenty-seven patients with measurable or evaluable, regionally advanced or metastatic head and neck cancer were given a combination of cyclophosphamide (C), Adriamycin (A), and cis-diamminedichloroplatinum (II) (P). Most patients had received extensive prior surgery and/or radiation therapy. Among 25 evaluable patients, the overall response rate was 64% (16/25) with 3/25 complete responders and 13/25 partial responders. The median survival for the entire group of 25 patients and the median response duration for the subset of 16 patients experiencing tumor regression were 8.1 and 7.0 months, respectively. Responders lived significantly longer than nonresponders (11 months vs. six months, P less than 0.01). According to covariate analysis, the difference seems to reflect the influence of response to treatment and not other confounding variables. Almost all patients experienced anorexia, nausea, vomiting, and a pervasive feeling of ill-health. In fact, six patients declined further treatment and five of these had objective tumor regressions. Recurrent disease was detected three months following discontinuation of chemotherapy in four of these five patients and seven months later in the fifth. Myelosuppression was clinically acceptable and there was in this dosage and schedule no evidence of hepatic or renal impairment. Although the CAP regimen has substantial antitumor activity, the program is clinically rigorous and should remain an investigational treatment modality at the present time.

Adolescent↗
PubMed1981

Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer.

Before the introduction of tamoxifen, diethylstilbestrol (DES) was widely considered to be the hormonal treatment of choice in postmenopausal women with advanced breast cancer. We performed a randomized clinical trial of these two agents to determine their relative efficacy and toxicity. The trial involved 143 evaluable patients, of whom 99 had received no prior systemic therapy and 44 had received previous chemotherapy. The regression rates (complete plus partial) were higher in patients receiving DES (41 per cent) than in those receiving tamoxifen (33 per cent), but not significantly so (P = 0.37). In patients who had had no prior systemic therapy, the rates were 44 per cent and 38 per cent, respectively (P = 0.55), and in those who had had previous chemotherapy, 32 per cent vs. 23 per cent (P = 0.50). Analysis of the time until treatment failure for the two treatment groups showed no significant difference (medians: DES, 142 days; tamoxifen, 171 days). Toxicity was greater in patients receiving DES; nine of 74 patients (12 per cent) discontinued therapy solely because of adverse reactions. Since there was no statistically significant difference in efficacy and since tamoxifen was less toxic, tamoxifen appears to be the preferred agent.

Aged↗