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Biomedical subjects

J U Gutterman

Publications and source records attributed to J U Gutterman.

At least 235 records · Page 13Linked to original sources

The use of leukocyte cell line culture supernatant for skin reaction testing in malignant melanoma.

A study was conducted to determine some of the potential applications of a human leukocyte culture supernatant or "lymphokine" preparation in cancer patients. The application evaluated in this study was the use of this preparation as a skin test reagent for evaluation of the inflammatory response following intradermal injection. The preparation was derived from the supernatant of a long-term cultured lymphoblastoid cell line with migration inhibition factor (MIF) and other lymphokine activities. Dose response, histology and toxicity studies were done in 53 patients with malignant melanoma stage IIIB and IV. A dose response curve was observed for both erythema and induration at 12 and 24 hours, but not at 48 hours. An optimal intradermal dose for eliciting inflammation was determined and found to be five units. Histopathological evaluation of biopsy specimens showed a mixed cell reaction including granulocytes, eosinophils, lymphocytes and monocytes differing in lymphocyte content from the classical delayed type hypersensitivity (DTH) reaction in man. Compared with the response to recall antigens, only a weak correlation with the DTH response to the recall antigens was found. Our results support the conclusion that lymphokines may be used in the future to evaluate the ability to develop nonspecific inflammation in cancer patients, and that this inflammatory response can be obtained in a number of patients no longer capable of responding to recall antigens.

Adult↗

Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG.

One hundred five patients with metastatic breast cancer were treated with 5-fluorouracil, Adriamycin, cyclophosphamide and BCG (FAC-BCG). The results were compared to those observed in a group of 44 patients treated with FAC chemotherapy alone. Although the overall response rates were similar (76% for FAC-BCG and 73% for FAC), the duration of remission was of 9 months for FAC and 14 months for FAC-BCG (p = 0.008). Similarly, survival of responding patients treated with FAC-BCG was significantly longer (24 months) than that observed in the chemotherapy alone treated group (15 months). There was no difference in survival or duration on study for nonresponders. Analysis of response rates by known prognostic factors was unrewarding. The duration of remission and survival, however, were significantly longer for patients with bone soft tissue involvement than for patients with visceral metastasis. Similarly patients with 1 or 2 metastatic sites survived significantly longer than those with more than 3 organ sites involved (p = 0.02). This chemotherapeutic combination is highly effective in inducing remissions. In addition, nonspecific immunotherapy with BCG appears to prolong duration of remission and survival for responding patients.

Adult↗

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↗

Combined chemoimmunotherapy and radiation therapy of inflammatory breast carcinoma.

Thirty-two patients with a diagnosis of primary inflammatory breast carcinoma were treated with combination chemoimmunotherapy consisting of 5-fluorouracil, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (FAC) plus BCG followed by radiation therapy. This group of patients was compared to a group of 32 consecutive historical controls treated with radiation therapy alone. The estimated mean disease-free interval for the FAC-BCG group was 16 months, compared to 9 months for the radiation therapy alone group (P less than 0.01). The estimated median survival for the FAC-BCG treated group was 24 months, compared to 18 months for the radiation therapy alone group (P = less than 0.03). The combined modality approach consisting of chemoimmunotherapy and radiation therapy significantly improved the disease-free interval and survival of patients with inflammatory breast carcinoma.

Adult↗

Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).

A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.

Antineoplastic Agents↗

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.

BCG Vaccine↗

A study of transfer factor for opportunistic infections in cancer patients.

Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of "opportunistic" infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation.

Adolescent↗

Human leukocyte interferon preparation blocks granulopoietic differentiation.

Since interferon administration in the treatment of some malignant conditions has been reported to cause leukopenia, we studied the effects of human leukocyte interferon preparation (HLIF) on myelopoiesis in vitro. The continual presence of HLIF in semisolid agar cultures caused a progressive decline in colony and a rise in cluster incidence with increasing concentrations of interferon. The total plating efficiency, however, remained nearly constant, regardless of the HLIF doses used. Morphological examination of the clusters demonstrated a progressively increasing percentage of immature granulocytic precursors with increasing HLIF concentrations. This suggests that HLIF causes leukopenia by blocking differentiation of marrow myeloid precursors.

Cell Aggregation↗

Prognostic factors in metastatic breast cancer treated with combination chemotherapy.

Six hundred nineteen patients with metastatic breast cancer, treated with a combination of 5-fluorouracil, Adriamycin, and cyclophosphamide, or close variations of this program, with or without immunotherapy were analyzed retrospectively to identify those host, tumor, or treatment characteristics that might be of prognostic importance in predicting response to chemotherapy and survival from onset of the 5-fluorouracil-Adriamycin-cyclophosphamide treatments. Primary tumor characteristics such as size of primary, number of axillary nodes involved, stage at diagnosis, and type of surgery used for primary treatment were not found to be of prognostic significance. Host characteristics such as age, menstrual status, or family history of breast cancer were similarly unrelated to outcome. Non-Caucasian patients had a lower response rate and somewhat shorter survival than did Caucasians. Pretreatment weight loss, poor performance status, and abnormal biochemical and hematological values were of adverse prognostic significance. An estimate of total extent of disease based on criteria for rating extent of involvement at 12 potential sites was a much more important prognostic factor related to response and survival than actual sites of involvement or the traditional "dominant site" classification. There was a trend, however, for patients with bone involvement to have a longer survival than did patients with metastases to other organ sites. Shorter survival times were observed among patients exposed to extensive prior radiotherapy and those who failed to respond to prior hormonal treatment. The prognostic variables identified in this paper should be used for the design and comparison of clinical trials in the future.

Adult↗

Intensive postoperative chemoimmunotherapy for patients with stage II and stage III breast cancer.

For the past 34 months, a combination of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in stage II and III breast cancer patients with positive axillary nodes. In the group of 131 patients receiving FAC-BCG, the estimated proportion remaining disease-free at 2 years from surgery was 91% compared to an estimated 69% in a group of 151 historical control patients (p less than .01). This advantage was statistically significant in all subgroups except for patients with primary tumor less than 3 cm and for patients with less than 4 positive nodes. Estimated 2-year survival rates were 9,6% for FAC-BCG patients and 86% for control (p = .02). Treatment was well tolerated. Adjuvant FAC-BCG seems effective in prolonging disease-free interval and early survival in patients with stage II and III breast cancer. Its long term efficacy will require longer follow-ups.

Adult↗

Disseminated BCG disease associated with immunotherapy by scarification in acute leukemia.

Disseminated BCG infection developed in a patient with acute leukemia receiving BCG immunotherapy by scarification. Predisposing factors included the underlying malignancy, intensive chemotherapy, and continuous high-dose corticosteroids. The scarification technique is safe; however, physicians should be alert to this syndrome as a cause of fever of unknown origin in cancer patients receiving BCG immunotherapy.

Aged↗

Immunotherapy with BCG administered by scarification: standardization of reactions and management of side effects.

The method of administering BCG by scarification is described in detail. A system of classifying the intensity of local reactions is proposed to standardize administration. The experience of the M.D. Anderson Hospital involving over 2700 patients is reviewed. Administration of BCG by scarification has been accomplished with safety and has been well tolerated and accepted. The most commonly observed side effects are discussed as well as their management.

Angina Pectoris↗

Randomized trial of protected environment--prophylactic antibiotics in 145 adults with acute leukemia.

One hundred and forty-five adults with acute leukemia were randomized to receive remission induction therapy in or out of a protected environment (PE) with prophylactic antibiotics orally (PA) or systemically (SA). Sixty-three patients were randomized in PE and 82 outside a PE. The proportion of patients who survived long enough to receive an adequate trial was higher in the PE (97%) than out (82%) (P = .01). The complete remission (CR) rate was 71% in and 43% out of the PE (P less than .01). Fifty-five patients received PA and 90 received SA. The CR rates were 61% and 45%, respectively. Of the 145 patients, 73 (50%) developed 102 episodes of major infections. Twenty-six of 63 patients in the PE developed major infection compared to 47 of 82 outside a PE (P = .08). The incidence rate of 13% fatal infections in a PE was significantly smaller than the 28% rate outside a PE (P = .04). The number of days with infections at less than 500 neutrophils/mm3 was also significantly lower inside a PE than outside (P less than .01). When comparing patients receiving SA or PA, there was no statistically significant difference in the incidence of infections. Forty-one patients received OAP Chemotherapy and 104 received adriamycin-OAP plus BCG. The CR rate on OAP was 44% compared with 60% on Ad-OAP + BCG. Infection rates were 76% and 40%, respectively (P less than .01). The median survival time was 72 weeks for patients in PE compared with 42 weeks for patients outside a PE (P less than .01). The prophylactic antibiotic regimens were well tolerated by most patients. This prospective randomized study has demonstrated statistically significant advantages for a lowered risk of fatal infection, higher CR rate and longer survival of patients treated in a PE with prophylactic antibiotics compared with patients treated in a conventional hospital room. Also, there was evidence for the superiority of adriamycin-OAP + BCG treatment compared with OAP.

Acute Disease↗