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Biomedical subjects

V Rodriguez

Publications and source records attributed to V Rodriguez.

At least 73 records · Page 4Linked to original sources

Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia.

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.

Adult↗

Neuroblastoma in the adult: effective combination chemotherapy.

Although neuroblastoma occurs most frequently in children, it also may occur in adults and has been considered of poor prognosis. Six adult patients (greater than 16 years of age) with widespread neuroblastoma diagnosed between 1974 and 1976 are described. Five were treated with a combination of cyclophosphamide, vincristine, adriamycin and dimethyl triazeno imidazole carboxamide (CYVADIC). The sixth received a similar regimen in which actinomycin D was substituted for dimethyl triazeno imidazole carboxamide (CYVADACT). There were two complete responses and three partial responses. The median duration of survival is in excess of 11 months. The results indicate that effective chemotherapy is now available for these patients and the achievement of remission and prolongation of survival are realistic goals in neuroblastoma.

Adolescent↗

Fever and infection in leukemic patients: a study of 494 consecutive patients.

All of the febrile episodes occurring in 494 adults with acute leukemia were reviewed. There were an average of 2.39 febrile episodes per patient and the patients spent 28% of their days in the hospital with fever. Sixty-four percent of the febrile episodes were due to infection. The most common types of infection were disseminated infection and pneumonia, which together accounted for 69% of the total episodes of documented infection. The etiologic agent was identified in 73% of the documented infections and gram-negative bacilli were responsible for the great majority. The most common gram-negative bacilli causing infection were Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. During the course of their leukemia, 31% of the patients had repeated episodes of infection caused by the same organism and 13% ahd repeated FUO's. Fever occurred most often when the patients had neutropenia (less than 500/mm3). The fatality rate from septicemia decreased from 84% in 1966 to 44% in 1972. The fatality rate for major infections caused by gram-positive cocci was 16%, for gram-negative bacilli was 37% and for fungi was 86%. Although infection remains a serious problem in leukemia patients, considerable progress has been made.

Acute Disease↗

Sequential chemoimmunotherapy of colorectal cancer: evaluation of methotrexate, Baker's Antifol and levamisole.

Fifty-two untreated patients with colorectal cancer were randomized to receive 5-fluorouracil (5-FU) alternating either with methotrexate (MTX) or Baker's Antifol (BAF) with or without the immunostimulant, levamisole (Program I). Fifty-five patients who had received prior treatment were randomized to receive methyl-CCNU (Me) with MTX or BAF (Program II). Fifteen of these patients had failed to respond to initial therapy with 5-FU plus MTX or BAF and subsequently received Me plus the alternate antifol. Overall response rate for each of programs I and II was 10%. The responses were 1/11 with 5-FU-MTX plus levamisole, 2/12 with 5-FU-MTX, 1/8 with 5-FU-BAF plus levamisole, 0/8 with 5-FU-BAF, 2/20 with Me-MTX and 2/21 with Me-BAF. The median survival times (MST) for patients receiving Programs I and II were 10 and 5 months, respectively. The MST for all patients receiving MTX was significantly longer than that of patients receiving BAF Survival was not influenced by levamisole administration. Both chemotherapy programs were well tolerated. The sequential administration of 4 active agents failed to improve the results of treatment of colorectal cancer.

Adolescent↗

Improvement in complete response rate, duration of response and survival with adriamycin combination chemotherapy for non-Hodgkin lymphoma: a prognostic factor comparison of two regimens.

The results of a chemotherapy regimen utilizing adriamycin in combination with vincristine, prednisone plus or minus cyclophosphamide (CHOP-HOP) for the treatment of non-Hodgkin lymphoma are compared to those of a non-adriamycin containing combination (COP). The complete remission (CR) rate of 67% for CHOP-HOP in malignant lymphoma, diffuse histiocytic type (MLDH) is superior to 33% obtained with COP. In malignant lymphoma, nodular poorly differentiated lymphocytic (MLNPD), the CR rate was: CHOP-HOP 83%, COP 44%. The prognostic factors for both treatment groups were compared and found to be similar. Thus, adriamycin appears to be responsible for this improvement in CR rate. When analyzed as a group, the patients treated with CHOP-HOP had a longer survival than those treated with COP. This difference was also evident in the subgroup of patients with MLDH. The smaller subgroup of patients with MLNPD treated with CHOP-HOP did not show a significant improvement in survival. A trend for longer duration of CR in both diffuse and nodular lymphomas was also observed, but this difference did not reach statistical significance possibly due to the smaller numbers of patients. Combination chemotherapy with adriamycin has resulted in a higher CR rate and survival for patients with non-Hodgkin lymphoma particularly for the subgroup of patients with MLDH.

Antineoplastic Agents↗

Carbenicillin plus cefamandole in the treatment of infections in patients with cancer.

The combination of carbenicillin plus cefamandole was administered to 88 patients with cancer during 116 evaluable episodes of fever. The overall response rate to carbenicillin plus cefamandole for the 116 episodes was 57%. There were 60 documented infections, of which 60% responded to this combination of antibiotics. The response rate was only 43% in patients with pneumonia. The etiologic agent was identified during 38 infections, of which 74% responded to carbenicillin plus cefamandole. Responses occurred less frequently in patients with neutropenia than in those without neutropenia and less frequently in patients whose infection was caused by organisms resistant to both antibiotics than in those with infection caused by organisms sensitive to one or both of the drugs. No side effects could be attributed to the antibiotic regimen.

Adolescent↗

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↗

Phase I study of maytansine using a 3-day schedule.

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to 60 patients as part of a phase I study. The doses given ranged from 0.01 (starting level) to 0.9 mg/m2 for 3 days. The toxic effects encountered consisted principally of nausea, vomiting, diarrhea, and occasionally, stomatitis and alopecia. Superficial phlebitis was also encountered and occurred when the drug was diluted in a volume of less than 250 ml. Myelosuppression occurred infrequently; it was almost regularly associated with abnormal liver function tests. Antitumor activity was detected in one patient each with melanoma, breast carcinoma; and head and neck clear cell carcinoma. Further studies are indicated with this compound since it has shown evidence of activity with little or no myelosuppression.

Blood Cell Count↗

Isophosphamide therapy for hematologic malignancies in patients refractory to prior treatment.

Isophosphamide was administered to 27 patients with acute leukemia and to 15 patients with malignant lymphoma refractory to primary therapy. The starting dose of isophosphamide was 1200 mg/m2 administered as a daily continuous infusion x 5 days; the courses of treatment were repeated every 2-3 weeks. Of the 27 patients with acute leukemia, four achieved complete remission, two achieved partial remission, and two achieved hematologic improvement. However, no responses occurred in ten patients with acute myelogenous leukemia (AML). Thus, the response rate was 47% (eight responses among among 17 patients, in patients with acute lymphoblastic leukemia and acute undifferentiated leukemia. Seven of the 15 patients with malignant lymphoma responded. Most responses (five of six patients) occurred in patients with diffuse histiocytic lymphoma. Twenty-one of the 42 patients had received prior therapy with cyclophosphamide and 12 of these patients (two with leukemia and ten with lymphoma) responded, thus suggesting that as in the treatment of L1210 leukemia, isophosphamide is effective for tumors resistant to prior cyclophosphamide therapy. No significant genitourinary toxicity occurred; however, myelosuppression became the dose-limiting toxicity. Isophosphamide is active in malignant lymphomas and acute leukemias (except AML) and may have a role in combination regimens for such diseases.

Acute Disease↗

Escherichia coli bacteremia in patients with malignant diseases.

Of 142 episodes of Escherichia coli bacteremia that were reviewed, appropriate antibiotics were administered during 98 episodes diagnosed premortem and 74 episodes (71%) responded. The highest cure rates were observed when the portals of entry were the urinary tract and soft tissues. Administration of adrenal corticosteroids did not affect the outcome of these patients. The patients' neutrophil counts at the onset and during infection were important factors in predicting survival. Septic shock occurred in 13% of all episodes, and only 11% of these patients responded. Of those patients who died, 63% died within the first 24 hours. Aminoglycosides, cephalosporins, and semisynthetic penicillins used alone or in combination offered optimal coverage.

Adolescent↗

Factors predicting for response and survival in adults with advanced non-Hodgkin's lymphoma.

Knowledge of the prognostic factors that characterize a disease can assist in planning and analyzing clinical trials. The present study was conducted to determine the characteristics related to response and survival in patients with stage III and IV non-Hodgkin's lymphoma who were treated with combinations of cyclophosphamide, vincristine sulfate, and prednisone. Considering each characteristic individually and using stepwise regression analysis, tumor bulkiness, prior therapy, sex, and pretreatment lymphocyte count were selected as the four most important prognostic variables. Tumor architecture (diffuse or nodular pattern) and cell type, hemoglobin level, and symptoms although not important in predicting response were found to be important in predicting survival. The hemoglobin level had only marginal importance in predicting response. Factors found not be important were age, stage, symptoms, cell type, nodularity, marrow involvement, prior extensive radiotherapy, and bone involvement. A logistic regression equation has been derived that can be used to predict response rate.

Cyclophosphamide↗

Gram-negative bacillary infections in cancer patients.

The majority of infectious complications in cancer patients are caused by Gram-negative bacilli. The most common organisms are Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. Sites of infection are related to the patients' underlying malignancies, but pneumonia and septicaemia occur most often. Important newer antibiotics for the therapy of these infections are aminoglycosides and semisynthetic penicillins. It is advisable to utilize combinations of antibiotics for serious infections in cancer patients, and therapy should be instituted promptly at the onset of infection.

Anti-Bacterial Agents↗

Sulfamethoxazole-trimethoprim for infections in cancer patients.

A combination of sulfamethoxazole and trimethoprim (Bactrim) was given orally to 35 cancer pattients with infections. Thirty-two patients did not respond to an initial antibiotic regimen that consisted primarily of carbenicillin disodium and an aminoglycoside. There were 18 single-organism, Gram-negative infections. The overall cure rate was 54%. The most common infection was pneumonia (47% responded to treatment). Eighty precent of the cases of septicemia were cured. The most common infecting organism was Klebsiella pneumoniae (45% with this infection responded). Eight cases of infection of unknown origin occurred (63% responded to treatment). Overall, 47% of the patients whose neutrophil count remained unchanged or decreased responded, while 61% of those whose neutrophil count remained unchanged or increased responded. There was no close correlation between the minimum inhibitory concentrations and the clinical responses. Sulfamethoxazole-trimethoprim orally is a well tolerated and effective form of antimicrobial therapy.

Administration, Oral↗

Comparison of lymphangiograms and gallium scans in the non-Hodgkin's lymphomas.

A total of 92 lymphangiograms (L.G.) and gallium scans (G.S.) done in 51 patients with non-Hodgkin's lymphoma were evaluated to assess their usefulness in detecting infradiaphragmatic disease. It was found that the correlation between both procedures was fairly good before treatment (85%) but decreased considerably after therapy. A significant number of patients persistently had positive L.G. after treatment, with a negative G.S. No histologic examination of tissues was performed, however, to confirm the radiographic findings. A higher number of equivocal G.S. were found both before and after treatment. No significant difference in correlation was found between the histiocytic and lymphocytic lymphomas but the former were found to have a striking frequency of negative L.G. and G.S. in the infradiaphragmatic area.

False Negative Reactions↗

Chemoimmunotherapy of metastatic large bowel cancer: nonspecific stimulation with BCG and levamisole.

The administration of two chemoimmunotherapy programs to 103 consecutive patients with metastatic colorectal cancer resulted in improved survival for patients who achieved either objective tumor regressions or disease stabilization for more than 8 weeks. Objective tumor regression was observed in 47% of patients treated with the Ftorafur-methyl-CCNU-methotrexate-Bacillus Calmette-Guerin (FTOR-MeM-BCG) program and in 34% of patients treated with the 5-fluorouracil-methotrexate-Baker's antifol (FU-M-BAF) +/- Levamisole program. The combinated median duration of survival for patients who achieved objective tumor regression and disease stabilization with FTOR-MeM-BCG was 13 months compared with 6 months for patients who had progression of disease (p = 0.001). The corresponding values for patients treated with FU-M-BAF +/- levamisole were 11 months and seven months, respectively (p = 0.001). While the role of BCG immunotherapy in these results remains speculative, the administration of levamisole immunotherapy did not appear to have influenced results significantly. Patients who presented at diagnosis with Dukes A, B and C lesions, and therefore had longer disease-free intervals, responded more frequently to chemoimmunotherapy and survived longer than patients who presented at diagnosis with Dukes D lesions. Similarly, greater antitumor effect was observed in patients with lower pretreatment plasma CEA levels evaluation of these pretreatment characteristics may have insignificant implications for the design of future clinical trials.

BCG Vaccine↗