Phase II study of recombinant gamma-interferon in patients with advanced nonosseous sarcomas.
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Adult↗
Biomedical subjects
S Frytak
Publications and source records attributed to S Frytak.
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↗
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↗
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↗
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↗
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↗
Phase II trial of diaziquone in malignant mesothelioma.
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Adult↗
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↗
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↗
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↗
Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.
Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen.
DNA, Recombinant↗
Metabolic studies of delta-9-tetrahydrocannabinol in cancer patients.
The metabolism of oral delta-9-tetrahydrocannabinol (THC) was studied in nine patients with gastrointestinal neoplasms receiving chemotherapy regimens containing 5-FU and semustine. Plasma levels of THC and its metabolites 11-OH-delta-9-THC (11-OH-THC) and 11-nor-9-carboxy-delta-9-THC (C-THC) were measured. Plasma levels of THC and its metabolites were quite variable among the patients studied. Plasma levels of THC and 11-OH-THC tended to peak at the same time; the C-THC levels peaked later and lasted much longer than the others. Mean half-lives of THC, 11-OH-THC, and C-THC were estimated to be 1.5, 2.1, and 4.4 hours, respectively. Multiple doses of THC did not produce a significant additive effect on the plasma concentrations of the biologically active metabolites THC and 11-OH-THC. No correlation between antiemetic effect or cannabinoid toxicity and plasma levels of the three metabolites could be made in this small number of patients.
Adult↗
Phase II study of diaziquone in patients with advanced carcinoma of the lung.
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Antineoplastic Agents↗
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↗
Phase II study on DON in patients with previously treated advanced lung cancer.
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Adenocarcinoma↗
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↗
Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.
One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.
Adenocarcinoma↗
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↗