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E J Freireich

Publications and source records attributed to E J Freireich.

At least 19 recordsLinked to original sources

Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine. A follow-up report.

Two hundred twenty-two patients with stage II or III breast cancer following regional therapy were treated with a combination of fluorouracil, doxorubicin hydrochloride (Adrimycin), cyclophosphamide, and BCG vaccine. At 54 months of study (median follow-up, 30 months), the estimated proportions remaining disease-free two and three years after surgery were 83%and 78%, respectively, in the chemotherapy group and 64% and 55%, respectively, in 151 historical control patients. Estimated two- and three-year survival rates were 93% and 89%, respectively, in the chemotherapy group and 84% and 58%, respectively, in the control patients. Congestive heart failure has developed in three patients, possibly related to the use of doxorubicin. Adjuvant chemotherapy with these drugs was effective in prolonging the disease-free interval and survival of patients irrespective of menopausal status, degree of nodal involvement, or stage of the disease.

Antineoplastic Agents

Oncology.

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Antineoplastic Agents

Continuous intravenous arabinosyl cytosine infusions delivered by a new portable infusion system.

Eighty-six patients with acute leukemia were given 116 continuous intravenous arabinosyl cytosine (Ara-C) infusions (for 24 to 432 hours) with a new portable infusion device. The infusor is powered by interchangeable elastomeric 25 ml balloon reservoirs loaded from standard syringes. The reservoir contents are discharged at nearly constant pressure through an adjustable resistance element, thereby providing flow rates from 0.4 to 2.0 ml/hour. Serum levels of labeled Ara-C delivered by the infusor were found to achieve steady-state therapeutic levels within 24 hours. The average-flow-rate-to-indicator-setting ratio determined for each infusion via scalp vein needles was 0.9 +/- 0.2. Delivery through catheters was more reliable and an average-flow-rate-to-indicator-setting ratio of 0.1 +/- 0.1 was observed. The therapeutic effectiveness of Ara-C in combination with other agents was not compromised by this delivery system. Eleven of 14 patients who received all their induction Ara-C through the infusor achieved complete remission.

Acute Disease

Treatment of acute leukemia in protected environment units.

Thirty evaluable patients with acute leukemia (AL), aged 14 to 48-year-old received remission induction chemotherapy on a protected environment-prophylactic antibiotic program. Twenty-seven (90%) of these patients achieved complete remission and 17 remained in complete remission for 1 to 22 months. Although these patients spent 36% of their time with neutrophil counts less than 100/mm3, they spent only 20% of their time with fever. Major infection was present during only 7% of the days when neutrophil count was less than 100/mm3. No patient died of an infectious complication during remission induction therapy.

Adolescent

Nodular malignant lymphomas: factors affecting complete response rate and survival.

The records of 109 patients with non-Hodgkin's lymphoma of nodular pattern were reviewed to determine which factors were associated with a favorable response to therapy and prolonged survival. A logistic regression model was utilized to identify the pertinent variables. Prognostic factors associated with a favorable response were, in order of decreasing importance: treatment with an Adriamycin combination regimen, absence of bulky tumor, and no exposure to prior chemotherapy. Thos associated with prolonged survival were: normal hemoglobin level, treatment with an Adriamycin combination regimen, female sex, and no prior exposure to therapy. Achievement of complete remission in these disorders resulted in a statistically longer duration of survival compared to partial responses or failures. Patients whose complete remission was induced with an Adriamycin-containing regimen and maintained with BCG immunotherapy had a significantly longer complete remission than those who did not receive BCG. Knowledge of these factors can be important in planning and analyzing future therapeutic trials.

Antineoplastic Agents

Phase II evaluation of vindesine in the treatment of colorectal and esophageal tumors.

A phase II study of vindesine was carried out in 33 patients with colorectal cancer and nine patients with esophageal cancer. With the exception of six previously untreated patients with esophageal cancer, all others were refractory to 5-FU-containing regimens, w,hich included vincristine in ten patients. The initial dose of vindesine was 4 mg/m2 administered intravenously over 30 min every 2 weeks. Tumor regression less than 50% was set patients (six colorectal and two esophageal) achieved minor responses. Prior treatment with vincristine did not seem to influence response to vindesine. In general, the treatment with vindesine was well tolerated. The hematologic toxicity was acceptable and manifested mainly as moderate and transient neutropenia. The major nonhematologic toxicity was peripheral neuropathy, which became limiting. It occurred in 33% of patients who received two or more courses of vindesine. Because of the apparent antitumor activity and dose-limiting neurotoxicity of vindesine in this sutdy, further investigations of this compound should be conducted in combination chemotherapy programs for patients with metastatic gastrointestinal cancers.

Adult

Protected environment-prophylactic antibiotic program for malignant lymphoma. Randomized trial during chemotherapy to induce remission.

Fifty-eight patients with malignant lymphoma were randomly allocated to receive three courses of chemotherapy to induce remission with CHOP-Bleo on the protected environment-prophylactic antibiotic (PEPA) program (30 patients) or as controls (28 patients). The complete remission rate for all patients was 74 per cent, for patients with diffuse histiocytic lymphoma 78 per cent and for patients with nodular poorly differentiated lymphocytic lymphoma 65 per cent. There were no significant differences in response rates and duration of responses between those on the PEPA program and control patients. The frequency of infection was significantly lower among the patients on the PEPA program, and dosage escalation of the chemotherapeutic agents was accomplished more often among these patients. Dosage escalation did not increase the complete remission rate, but it did reduce the relapse rate and signficantly reduced the fatality rate. The duration of remission and survival was significantly longer for those patients who received dosage escalation.

Adolescent

Effects of time, platelet concentration, and sex on the human platelet aggregation response.

The platelet aggregation responses induced by adenosine diphosphate (ADP) and collagen were characterized by parameters defining rate and extent of reaction. Values were compared on the basis of platelet concentration, time elapsed between sample collection and test performance, and sex of donors. Rate and extent of aggregation varied as a function of platelet concentration. Maximal responses were obtained for platelet concentrations greater than 100,000/microliter. Results from samples processed after 90 min of incubation at room temperature were consistently and significantly lower than those obtained from samples processed immediately. ADP-induced aggregation responses elicited by samples from male and female normal donors differed significantly. This indicates that comparisons between normal and patient results should be made with sex-matched individuals to avoid erroneous interpretations.

Adenosine Diphosphate

Ethical considerations in cancer chemotherapy.

Cancer treatment has improved dramatically in the recent past. As a consequence, the range of choices has been greatly broadened. With a much larger range of choices and a larger range of treatment disciplines available, decisions regarding treatment create major ethical burdens for the physician and for the patient. The participation of the patient in such choices improves the ethical posture of the therapist, whenever that is possible, and also improves the probability that the best treatment will be administered. Clinical research plays an important role in cancer treatment, not only in the the discovery of new treatment, but in the provision of the best possible care for patients participating in such research. At all levels of clinical research, such treatment has the potential for being the best available treatment when conducted in the most professional manner. While poor clinical research, like poor conventional treatment, certainly exists, it is nonetheless true that clinical research has a permanent place in cancer treatment and provides an important alternate to cancer quackery. Virtually every patient with a malignant disease has some effective treatment available to him, even in the most hopeless circumstance, where the Phase I type of clinical investigation still offers significant opportunity and hope.

Disclosure

Complete remissions in metastatic breast cancer treated with combination drug therapy.

One hundred sixteen patients with metastatic breast cancer who achieved complete remission with combination chemotherapy were analyzed to ascertain the factors that affect the duration of complete remission and the patterns of relapse. The median duration of complete remission was 17 months. Disease recurred in 81 patients (70%) at periods ranging from 3 to 44 months after achievement of complete remission. The duration of complete remission was inversely related to the bulk of metastatic tumor. Twenty-three patients treated with combined oophorectomy and chemotherapy experienced the longest remissions (median duration of 33 months); only eight (35%) of them have relapsed. Seventy-six percent of the relapses occurred in previously known sites of tumor involvement; most of the remainder involved the brain. The short duration of complete remissions and tendency to relapse in sites of initial involvement suggest that patients with metastatic breast cancer who achieved complete remission with combination chemotherapy still had substantial residual tumor. Consolidation treatments, using hormonal therapy and non-cross-resistant chemotherapy along with irradiation to initial sites of metastases, whould be investigated to ascertain their usefulness in prolonging the remissions.

Adult

Results of a phase II study of maytansine in patients with breast carcinoma and melanoma.

During the phase I study of maytansine at our institution, some activity was observed against breast carcinoma and melanoma. A phase II study was thus initiated to more thoroughly investigate the activity of this drug against these two tumors. In 33 evaluable patients with melanoma, no complete or partial responses were observed. Twenty-one evaluable patients with breast cancer were entered and only one response (partial) was seen. The toxicity was similar to that observed in the phase I study and consisted mainly of diarrhea, paresthesias, phlebitis, and flu-like symptoms. Myelosuppression was infrequent and was short-lived when it occurred.

Breast Neoplasms