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Biomedical subjects

E T Creagan

Publications and source records attributed to E T Creagan.

At least 73 records · Page 4Linked to original sources
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

Phase I study of two schedules of teroxirone.

Two schedules of teroxirone, a triazine triepoxide, were evaluated in a phase I study. Twenty-six patients were treated on 1 day every 5 weeks at doses of 36-2250 mg/m2. At doses greater than or equal to 1500 mg/m2, severe thrombophlebitis was seen without cytotoxic effect, and this schedule was closed. Twenty-seven patients were treated on 5 days every 5 weeks at daily doses of 16-450 mg/m2. Mild thrombophlebitis and moderate leukopenia were encountered. For phase II studies, a dose of 375 mg/m2 X 5 every 5 weeks is recommended. Pharmacologic studies showed rapid plasma elimination, which suggests the agent's possible usefulness for regional infusion.

Antineoplastic Agents↗
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

Phase II study of the three-drug combination of mitomycin C, CCNU, and methotrexate (MCM) in advanced non-small cell lung cancer.

Ninety-two patients with advanced non-small cell lung cancer, 51 without prior chemotherapy exposure, were treated with the combination of mitomycin C, lomustine (CCNU), and methotrexate (MCM). Overall, the regression rate was 33%, the median regression duration 4.9 months, and the median survival 4.9 months. Patients with ECOG performance scores (PSs) of 0-1 had a statistically significant higher regression rate than did patients with ECOG PSs of 2-3 (43% versus 15%; p = 0.005) as did patients without prior chemotherapy (41% versus 22%; p = 0.05). Cell type and prior chemotherapy exposure did not affect regression duration, time to progression, nor survival. Subjective toxicity was quite acceptable. Cumulative myelosuppression was the most significant objective toxicity. MCM is a relatively effective combination chemotherapy regimen, even in patients with prior chemotherapy exposure (predominantly doxorubicin and cisplatin-based chemotherapy).

Adult↗
PubMed1986

Differing response rates and survival between squamous and non-squamous non-small cell lung cancer. Comparison of CAP versus MAP.

One hundred and thirty patients with advanced non-small cell lung cancer were treated in a randomized study with either CAP (cyclophosphamide, doxorubicin, and cisplatin) or MAP (mitomycin C, doxorubicin, and cisplatin). Among all patients, regardless of cell type, the regression rate was slightly higher for MAP (46%) than CAP (34%) but no differences were detected in time to progression and overall survival. However, differences were apparent by treatment when patients were divided into two groups: squamous cell (SQC) and non-squamous cell (non-SQC). MAP, compared to CAP, was associated with a significantly superior regression rate (60% vs. 33%), time to progression, and overall survival in SQC. On the other hand, CAP, compared to MAP, was associated with a significantly longer overall survival in non-SQC. This apparent difference among subtypes of non-small cell lung cancer in response to chemotherapy regimens differing only in one drug, if confirmed, will need to be kept in mind in designing future studies.

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

Phase I trial of parenteral 6-thioguanine given on 5 consecutive days.

For almost 30 years, 6-thioguanine (6-TG) has been administered p.o. for treatment of various human cancers, especially leukemias, even though the systemic availability of the drug given p.o. is known to be low and highly variable. Parenterally administered 6-TG has been studied in detail in humans only on a single-day intermittent schedule, although multiple-day intermittent schedules are known to produce maximal cytotoxic effects in several animal species. To develop a multiple-day regimen for parenteral 6-TG therapy, we carried out a dose-seeking and pharmacokinetic study of the drug given i.v. daily for 5 days in patients with various refractory advanced solid tumors. Dose-limiting myelosuppression without other significant toxicity occurred at 55-65 mg/m2 daily for 5 days. After i.v. administration at 65 mg/m2, the mean peak plasma concentration of 6-TG ranged from 6-10 microM. These concentrations are 8-300 times greater than peak plasma concentrations of 6-TG in plasma reported to occur after p.o. administration at 100 mg/m2. We suggest that the antitumor activity of 6-TG be reassessed against human cancers in regimens of i.v. administration on multiple-day intermittent schedules.

Adult↗
PubMed1985

High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison.

It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy.

Aged↗
PubMed1985

Magnetic resonance imaging for neurotoxicity in long-term survivors of carcinoma.

Neurotoxicity is a potential complication of combined chemotherapy and whole-brain radiotherapy in long-term survivors of carcinoma. Clinical features of this neurotoxicity are similar to those manifested in the leukoencephalopathy of pediatric patients with leukemia who have been treated prophylactically with whole-brain radiotherapy and chemotherapy. Magnetic resonance imaging, because of its ability to distinguish cortical gray matter and white matter and its utility for studying demyelinating diseases, was used in the assessment of five long-term survivors of carcinoma who had clinical evidence of neurotoxicity. On magnetic resonance examinations, all five patients had profound abnormalities in the periventricular white matter. These changes were considerably more pronounced than those seen on computed tomographic scanning. Thus, magnetic resonance imaging may serve as a useful procedure for early detection of neurotoxicity in patients with carcinoma who have received cerebral radiotherapy and chemotherapy.

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↗
PubMed1985

Continuous five-drug versus alternating three-drug and two-drug chemotherapy after five-drug or three-drug induction in extensive small cell lung cancer.

Fifty-six patients with extensive small cell lung cancer were treated with vincristine, doxorubicin, cisplatin, etoposide, and cyclophosphamide in a prospective randomized trial using all five drugs together or as three-drug (cisplatin, etoposide, cyclophosphamide) and two-drug (doxorubicin, vincristine) combinations given sequentially, then alternatively. The five-drug combination was associated with a higher overall regression rate (p = 0.03), higher complete regression rate (p = 0.09), prolonged time to first progression (p = 0.03), more nervous system initial failures (p = 0.07), more anemia requiring transfusion (p = 0.04), but no prolongation of overall survival (median 332 days for five-drug, median 303 days for three-drug and two-drug). Until more and better chemotherapeutic agents become available, little or no advantage is likely to be gained for patients with small cell lung cancer given sequential, or alternating chemotherapy.

Adult↗