[Current status of the treatment of recurrent acute myeloblastic leukaemia in adults (author's transl)].
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Aminoacridines↗
Biomedical subjects
F Cabanillas
Publications and source records attributed to F Cabanillas.
Initial experience with AMSA as single agent treatment against malignant lymphoproliferative disorders.
Thirty previously treated adults with lymphoma received AMSA as single agent therapy. All patients had previously received adriamycin-containing chemotherapy regimens and either failed to respond initially or responded but subsequently relapsed. The dose used was 40 mg/sq m.i.v. daily x3. For patients with compromised marrow reserve or elevated bilirubin, a 25% reduction was used. Ten of 30 patients achieved an objective response (3 CR, 3 PR, and 4 less than PR). Of the 3 patients achieving a complete remission, 2 with histiocytic lymphoma remain in remission and are currently off treatment at 14+ and 18+ mo. The response rate to AMSA was found to correlate with the type of response to frontline therapy and also with the number of previous relapses. Complete remissions on AMSA were only seen in patients who had achieved a CR on frontline treatment and who were treated on their first relapse. AMSA is an active drug against malignant lymphoma and deserves further investigation.
Aminoacridines↗
Management with chemotherapy only of stage I and II malignant lymphoma of aggressive histologic types.
Thirty patients with clinical stage I-II malignant lymphoma of aggressive histologic types (histiocytic, undifferentiated, and mixed) were treated with chemotherapy alone. Of 25 patients with measurable disease, 22 (88%) achieved a complete remission. The remaining five patients had been rendered disease-free at the time of excisional biopsy; for this reason, they are considered evaluable only for duration of disease-free survival. Of the 27 patients who achieved disease-free status, 23 (85%) remain free of any evidence of disease. All eight patients with stage I disease and 15 of the 19 patients with stage II disease remain free of disease. The use of clinical instead of surgical staging, followed promptly by systemic treatment with combination chemotherapy, results in a substantial cure rate and avoids the undesirable morbidity and treatment delay associated with laparotomy. The results of this approach compare favorably with those obtained by radiotherapy alone or with combined radiation and chemotherapy for surgically staged patients.
Abdominal Neoplasms↗
Intensive induction chemotherapy of extensive small cell bronchogenic carcinoma in protected environment--prophylactic antibiotic units. A preliminary report.
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Adult↗
Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma.
Thirty-eight patients with advanced breast cancer, multiple myeloma, and malignant lymphoma were treated with partially purified (about 0.1%) leukocyte interferon. Patients were treated with a remission-induction schedule of 3 million to 9 million antiviral units daily intramuscularly for 4 to 26 weeks. Responding patients were maintained on a schedule of 3 million U three times weekly. Tumor regression was observed in seven of 17 patients with breast cancer. Six of 10 patients with multiple myeloma responded with a decrease of at least 50% in serum myeloma protein levels or Bence Jones protein excretion. Six of the 11 lymphoma patients achieved tumor regression. Complete remissions occurred in two patients. Of the 19 responding patients, five remain on study for 52 to 63 weeks. Toxicity included low-grade fever, fatigue, anorexia, and partial alopecia. Myelosuppression (lowest median leukocyte count, 2500/mm3; granulocytes, 1300/mm3) occurred in most patients. On the basis of this pilot study, we conclude that leukocyte interferon can induce tumor regression in patients with advanced cancer.
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↗
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↗
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↗
Central nervous system relapse in malignant lymphomas: risk factors and implications for prophylaxis.
The records of 292 patients with malignant lymphoma other than Hodgkin's disease, registered in our protocols from 1967 to 1977, were reviewed to identify those with central nervous system (CNS) involvement. Thirty-one patients were encountered with this complication, an incidence of 11%. Patients with a diffuse histology had a higher frequency of CNS recurences (27/174 = 16%) in contrast to only 4/118 (3%) for those with nodular types. However, if only patients with diffuse histology in CR are considered, the frequency of CNS relapse is 13.5% (13/98). The risk factors that predict for the development of this complication were studied using multivariate analysis. Diffuse poorly differentiated lymphocytic and diffuse undifferentiated lymphomas were found to be associated with a high risk of CNS relapse. Prior chemotherapy, bone marrow involvement, age less than 35, and extranodal disease were also identified as high-risk factors. Using the information generated by a logistic regression model, patients with malignant lymphoma of diffuse type can be classified into three categories when first seen: low-risk group, intermediate, and high-risk group. CNS prophylaxis is recommended for the intermediate and high-risk group, while only close follow-up is advised for the low-risk group patients who have one adverse characteristic.
Adult↗
Effective combination chemotherapy of adult malignant histiocytosis (histiocytic medullary reticulosis).
Adult malignant histiocytosis, also known as histiocytic medullary reticulosis, has been, in the past, considered a very aggressive disorder usually resistant to chemotherapy. Management in the past has included either single agent therapy or splenectomy. Recently, several cases have been reported that have responded favorably to combination chemotherapy. This paper reports on our experience with combination chemotherapy for this disorder. Of three patients treated, all three responded with a complete remission and two remain alive and free of disease at the present time. The outlook for patients with this diagnosis appears to be changing favorably with the advent of new treatment regimens.
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↗
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↗
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↗
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↗
Combination chemotherapy ("CHOP-Bleo") in advanced (non-Hodgkin) malignant lymphoma.
Forty-seven adults with advanced malignant lymphoma (the majority in stage IV) were treated with a combination of cyclophosphamide, hydroxyldaunorubicin (Adriamycin), vincristine (Oncovin), prednisone, and bleomycin (CHOP-Bleo). The complete remission (CR) rate was 66%. The overall response (complete + partial remission) was 92%. The CR rate in patients with diffuse histiocytic lymphoma (DHL) was 69%. Only 3 of the 18 patients with DHL in CR have relapsed; the projected median duration of response was calculated to be greater than 2 yr. In patients with nodular poorly differentiated lymphocytic lymphoma (NPDL), the CR rate was 62%. One of the eight patients with NPDL in CR has relapsed; the projected median duration of complete response will be greater than 4 yr. The median survival for all patients entered in this study has not been reached; however, it was estimated that it will be greater than 3 yr. The survival curves became flat at 70 wk for the patients with DHL and at 1 yr for the patients with NPDL. Major complications during chemotherapy with CHOP-Bleo were myelosuppression and alopecia. Only six severe infections occurred during myelosuppression. No hemorrhagic problems were observed. This study indicates that combination chemotherapy with these agents is effective in increasing the CR rate and survival in patients with diffuse histiocytic lymphoma. In patients with NPDL, further observation will be needed to assess the effect of this combination on survival.
Adult↗
Current status of chemotherapy of solid tumors.
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Humans↗
Nephrotoxicity of combined cephalothin-gentamicin regimen.
Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.
Acute Kidney Injury↗
Chemotherapy as definitive treatment of stage I-II large cell and diffuse mixed lymphomas.
Combination chemotherapy with adriamycin-containing regimens is effective in the management of advanced lymphomas. In view of this, we treated 43 patients with clinical stage I-II large cell or diffuse mixed lymphoma with chemotherapy. Routine staging laparotomies were not done and radiotherapy was not used in these patients. The CR rate for the combined stage I-II presentations is 90%. Of 11 patients with stage I presentations, only one has relapsed (at 64 months), and he expired 11 months after the recurrence. Of the 28 patients with stage II presentations who achieved a CR, seven have relapsed but three of these have achieved a second CR and remain in remission. Late relapses were common in this group of stage I-II presentations. Four of eight relapses occurring in patients who achieved disease-free status took place greater than 24 months after initiation of therapy. Chemotherapy alone appears to be adequate for treatment of stage I large cell lymphoma, although larger numbers of patients might be required to definitely make this conclusion. Close to 2/3 of patients with stage II presentations appear to have been cured with the use of chemotherapy alone. The failures occurred mostly in those with bulky disease. It is possible that radiotherapy given after chemotherapy could consolidate these bulky areas of disease and thus prevent local relapses.
Antineoplastic Combined Chemotherapy Protocols↗