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Biomedical subjects

H J Long

Publications and source records attributed to H J Long.

At least 55 records · Page 3Linked to original sources
PubMed1987

Three consecutive phase II studies of recombinant interferon alfa-2a in advanced malignant melanoma. Updated analyses.

In three consecutive Phase II trials of recombinant interferon alfa-2a (rIFN alfa-2a; Roferon-A Hoffmann-La Roche, Nutley, NJ) involving 96 patients with advanced malignant melanoma, an overall response rate of 22% was observed. For all study participants, the median time to disease progression was 1.7 months, and the median survival was six months. Most regressions occurred within one month of commencing therapy, were usually limited to soft tissue metastases, and were transient. However, responses in three patients were long term, lasting 32+, 36+, and 41+ months. A thrice weekly intramuscular dose of 50 x 10(6) U/m2 produced an intolerable flulike illness concomitant with a median weight loss of 5.6 kg. The addition of cimetidine to the same dose in 35 patients was of no therapeutic value. A dose of 12 x 10(6) U/m2 produced clinically acceptable toxicities, and a median weight loss of 2.1 kg. There was no apparent dose response relationship, nor were there any obvious sequelae from antibody formation to interferon alfa-2a. As single agent therapy in malignant melanoma, interferon alfa-2a was only marginally useful in most patients. Nevertheless, combination regimens of this agent with cytotoxic agents, alternative molecular species of interferon, and lymphokines, notably tumor necrosis factor, offer a conceptually intriguing dimension in the design of future clinical trials.

Adjuvants, Immunologic↗
PubMed1987

Lack of value for cisplatin added to mitomycin-doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial.

Fifty-five patients with metastatic carcinomas of unknown primary site (50 adenocarcinomas) were randomized, after stratification, to treatment with either mitomycin and doxorubicin (MA) or mitomycin, doxorubicin, and cisplatin (MAP). There was a moderate but nonsignificant improvement in regression frequency (14 vs. 27%) and a slight but also nonsignificant worsening of survival (median 5.5 months vs. median 4.6 months) by the addition of cisplatin at 60 mg/m2 to the MA regimen.

Adult↗
PubMed1987

Phase I and pharmacokinetic study of menogaril administered as a 72-hour continuous i.v. infusion.

Menogaril is a new anthracycline analog of nogalamycin. When administered as a 72-hour continuous iv infusion the dose-limiting toxic effect of menogaril was venous irritation at dose levels that cause only mild leukopenia and minimal gastrointestinal toxicity. Pharmacokinetic studies showed that the rise in plasma concentration during infusion was first-order, with a half-life of 11.9 hours. Total-body clearance of menogaril was 204 ml/minute/m2. There were no detectable metabolites of menogaril in plasma. Urinary excretion of unchanged menogaril was 17.3% of the dose and N-demethylmenogaril was 0.5% over 72 hours. Since menogaril does not appear to be metabolized, a high degree of tissue binding is likely.

Adult↗
PubMed1987

Phase II study of recombinant interferon-gamma in patients with disseminated malignant melanoma.

Twenty-eight patients with disseminated malignant melanoma received daily im therapy with recombinant interferon-gamma. The dose was 0.25 mg/m2 on Days 1-7 followed by a daily dose of 0.5 mg/m2 if tolerated. Among 27 patients, we observed three objective partial regressions (8.3, 3.7, and 3.9+ months). The median leukocyte count nadir was 2.5 X 10(3)/mm3 (range, 1.4-5.1). Constitutional symptoms included moderate to severe fever greater than 37 degrees C (100%), fatigue (59%), chills (37%), and mild to moderate myalgias (64%). Recombinant interferon-gamma produces manageable side effects but limited efficacy as employed in this study.

Adult↗
PubMed1987

Pilot study of cyclophosphamide plus carboplatin in advanced ovarian carcinoma.

Six patients with histologically proven stage III-IV ovarian carcinoma received carboplatin (CBDCA) (150 mg/m2) plus cyclophosphamide (1000 mg/m2) monthly for 1 year unless disease progressed earlier. Six other patients received CBDCA (225 mg/m2) with the same cyclophosphamide dose monthly. Continued treatment with the higher CBDCA dose was not tolerable because of myelosuppression, but no other dose-limiting toxic effect was observed. Complete tumor regression was proven at secondary laparotomy in six of the 12 patients, and five of these remain disease-free from 26+ to 28+ months after beginning chemotherapy.

Aged↗
PubMed1986

Recombinant leukocyte A interferon (rIFN-alpha A) in the treatment of disseminated malignant melanoma. Analysis of complete and long-term responding patients.

Ninety-six patients with disseminated malignant melanoma received thrice weekly intramuscular injections of leukocyte A recombinant interferon (rIFN-alpha A, Roferon-A, Hoffmann La Roche) at doses of 12 X 10(6) U/m2 or 50 X 10(6) U/m2 with or without cimetidine as an immunorestorative agent. Four patients, two with prior chemotherapy, demonstrated either a complete response (3 months, soft tissue metastasis) or exceptionally durable response durations (months) of 29+ (soft tissue; lung lesion), 31+ (soft tissue), and 35+ (soft tissue; liver lesions). None of these patients had particularly characteristic clinical parameters. As noted previously, using chemotherapy, a small proportion of patients with advanced malignant melanoma, despite prior therapy, may achieve prolonged objective regression with rIFN-alpha A.

Adult↗
PubMed1986

Phase II study: the combination DTIC, BCNU, actinomycin D, and vincristine in disseminated malignant melanoma.

Thirty patients with disseminated malignant melanoma received the combination DTIC, BCNU, actinomycin D, and vincristine. The objective response rate was 17 percent concomitant with moderate-to-severe nausea and vomiting in 80 percent of patients. Hematologic toxicity was transient. In the dose and schedule that we used, the four-drug regimen does not offer meaningful benefit for patients with advanced melanoma.

Adult↗
PubMed1986

Evaluation of bisantrene administered by 72-hour infusion in women with metastatic breast cancer.

Bisantrene was administered by 72-h continuous infusion at a dosage level of 240 mg/m2 to 17 patients with metastatic breast cancer who had received only one prior chemotherapy regimen and no prior doxorubicin. Three patients (18%) achieved partial regressions lasting 51, 106, and 213 days. For all patients, the median time to disease progression was 83 days and median survival was 280 days. Eleven patients received doxorubicin after removal from protocol and were evaluable for response, and four (36%) achieved a partial regression. We conclude that bisantrene administered by the method we employed is not associated with substantial clinical benefit in this population of patients.

Adult↗
PubMed1986

Phase I study of recombinant leukocyte A human interferon combined with BCNU in selected patients with advanced cancer.

Interferons manifest diverse immunomodulatory and antiproliferative characteristics. Since their spectrum of toxicities includes primarily fatigue and anorexia rather than the myelosuppression concomitant with cytotoxic therapies, it is conceptually appealing to combine both modalities. We conducted a phase I trial among 18 patients using the combination of leukocyte A recombinant interferon (IFN-rA) and BCNU. The intramuscular (IM) IFN-rA dose for the initial 12 patients was 12 X 10(6) U/m2 three times a week for an anticipated duration of 12 weeks. Among these patients, we escalated the monthly intravenous (IV) BCNU dose from 50 mg/m2 to 150 mg/m2. Six subsequent patients received IFN-rA 12 X 10(6) U/m2, days 1 to 3, and BCNU 150 mg IV on day 3 of each monthly cycle. Dose-limiting toxicities from both regimens were fatigue and myelosuppression. We recognize the limitation of small sample sizes. Nevertheless, in the absence of a significant number of life-threatening toxicities, it appears that near maximal doses of BCNU and concomitant IFN-rA can be administered with safety in an outpatient setting.

Adult↗
PubMed1986

Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer.

A randomized clinical trial was performed to compare the efficacy of tamoxifen (TAM) alone with that of TAM plus aminoglutethimide (AG) and hydrocortisone (HC). Patients failing TAM could receive AG and HC. Objective responses to therapy were seen in 21 of 49 TAM patients (43%) and 25 of 51 TAM, AG and HC patients (49%). Time to disease progression and survival distributions were not significantly different between the treatment arms. Toxicity was greater for patients treated with TAM, AG, and HC and the trial was discontinued early for this reason. Twenty-four patients received AG and HC after TAM therapy and three (12%) achieved a response. We conclude that the combination of TAM, AG, and HC is not recommended over TAM alone because toxicity appears to outweigh any potential therapeutic advantage.

Adult↗
PubMed1986

Phase II trials of recombinant leukocyte A interferon in disseminated malignant melanoma: results in 96 patients.

Ninety-six patients with advanced malignant melanoma received thrice weekly im recombinant leukocyte A interferon (Roferon-A) in three consecutive phase II trials utilizing doses of 12 X 10(6) U/m2, 50 X 10(6) U/m2, and 50 X 10(6) U/m2 plus cimetidine. The overall response rate was 22%, with median times to disease progression and survival of 3.9 and 11.3 months, respectively. For all study participants, the median times to disease progression and survival were 1.5 and 5 months, respectively. Most regressions occurred within the first month of treatment and were predominantly in soft tissue, although three patients are responding 2-3 years after onset of treatment. The most noteworthy toxic effects included a flu-type illness, anorexia, and fever (38.3-39.4 degrees C). The median weight loss was 2.1 kg on the low-dose regimen and 5.6 kg on the high-dose program. Recombinant leukocyte A interferon in the dosages and schedule that we used has definite but limited efficacy for patients with disseminated malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Ineffectiveness of tamoxifen in advanced endometrial carcinoma after failure of progestin treatment.

Between May 1980 and November 1983, 46 eligible patients with advanced, objectively evaluable endometrial carcinoma were treated with tamoxifen, 10 mg twice daily. Twenty-two of the patients had previously received progestational agents. None of the progestin-refractory patients experienced tumor regression on tamoxifen treatment, while five of the 24 previously untreated with progestins did experience tamoxifen-induced tumor regression. Of the five patients previously treated with cytotoxic drugs, only one experienced objective tumor regression on tamoxifen. Although 28 of these 46 patients were completely ambulatory at the beginning of tamoxifen treatment, only 26% were alive 1 year later; median survival for the entire group was only 120 days. Tamoxifen in this dose cannot be recommended routinely as effective secondary treatment for patients with progestin-refractory advanced endometrial carcinoma.

Aged↗
PubMed1985

Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma.

Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively.

Administration, Oral↗
PubMed1984

Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma.

Thirty-one patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 50 X 10(6) units/m2 three times weekly for a planned treatment duration of 3 months. Seven objective regressions (23%), which ranged in duration from 3 to 11.2+ months, were observed. Forty-two percent of 12 patients who were fully active (Eastern Cooperative Oncology Group [ECOG] performance score, 0) responded compared to 11% of 19 patients with impairment of performance status (ECOG, 1-3). Prior chemotherapy did not influence response rate. For all patients the median time to progression and of survival was 2 months and 6 months, respectively. Four patients had partial regressions in soft tissue (3, 4.6 months), pulmonary (7 months), and prostatic lesions (3 months). The latter was biopsy-proven and assessed by serial computerized tomography (CT) scans. Three had complete regressions of soft tissue disease (2 patients, 6.4 and 10+ months each), and liver involvement (11.2+ months). The major toxicities were moderate to severe fatigue (87%), anorexia (58%), and confusion (23%). Performance score deteriorated in 84% of patients during the time they were receiving rIFN-alpha A. Among the 13 patients whose tumors did not progress for at least 12 weeks, 7 required dose reductions or termination of treatment due to toxicities. Hematologic and hepatic toxicity was transient and of little clinical significance. The study indicates that rIFN-alpha A has some antitumor activity accompanied by difficult side effects in patients with disseminated malignant melanoma.

Adult↗
PubMed1984

Dose-response relationships of chronic adriamycin toxicity in rabbits.

Doxorubicin was administered chronically to 55 female New Zealand White rabbits in order to determine a chronic dose-response relationship for doxorubicin-induced cardiomyopathy, skeletal myopathy and nephropathy. Systolic time interval recording as a measure of cardiac function in doxorubicin-induced cardiomyopathy in the rabbit is compared to histologic grading of the cardiomyopathy. Histologic evidence of cardiomyopathy was not seen at cumulative doses less than 100 mg/m2 but incidence and severity of cardiomyopathy increased with increasing doxorubicin dosage. The most severe lesions were seen at cumulative doses in excess of 400 mg/m2. The dose-response of skeletal myopathy paralleled that of cardiomyopathy but the severity of histologic abnormalities and the incidence of skeletal myopathy was less than half that of cardiomyopathy at all dose levels. Nephropathy was a consistent finding at cumulative doses of doxorubicin in excess of 100 mg/m2.

Animals↗