mitoguazone and Hodgkin-Disease

Methylglyoxalbisguanylhydrazone or MGBG is an agent with a unique mechanism of action (polyamine biosynthesis inhibition). MGBG was discarded in the 1960s because of severe mucositis and other toxicities. New clinical trials in the late 1970s and early 1980s utilized weekly administration and indicated MGBG had significant activity in patients with chemotherapy-refractory Hodgkin's and non-Hodgkin's lymphoma. In addition, some activity was noted in patients with head and neck, prostate, esophageal, and endometrial cancer. The toxicities on the weekly schedule were minimal and no myelosuppression was noted. Based on MGBG's spectrum of antitumor activity and its activity in severely debilitated patients, we hypothesize that MGBG may have greater antitumor activity in patients who are malnourished (possibly based on polyamine depletion). MGBG is a good candidate for treatment of AIDS-associated NHL because it has proven activity in patients with NHL which is not associated with AIDS, crosses the blood brain barrier, is non-myelosuppressive, and appears to work in patients with inanition (no polyamines available to reverse MGBG's antitumor effects). Clinical trials are ongoing to determine the activity of MGBG in AIDS-associated NHL and other diseases. Based on encouraging initial results, it appears MGBG may become part of our therapeutic armamentarium.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biogenic Polyamines; Hodgkin Disease; Humans; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoguazone

Treatment of disseminated Hodgkin's disease still fails in about 50 percent of the cases. The prognosis is poorer in case of early relapse or when the disease is refractory to first-line therapy from the start. Second- or third-line chemotherapy regimens have given rather disappointing results with a complete remission rate usually around 30 percent and a small number of cures. The indications for radiotherapy in localized lymph node relapses remain to be precisely determined. Based on the theoretical dose-effect concept, high-dose chemotherapy followed by autologous bone marrow transplantation increases the number of prolonged complete remissions in patients who respond to salvage chemotherapy. A wider use of haematopoietic growth factors should reduce the toxicity of this treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Dacarbazine; Doxorubicin; Epirubicin; Etoposide; Hodgkin Disease; Humans; Ifosfamide; Mechlorethamine; Melphalan; Methotrexate; Mitoguazone; Prednisone; Procarbazine; Remission Induction; Transplantation, Autologous; Transplantation, Homologous; Vinblastine; Vincristine

To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment.. Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT.. With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival.. Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Male; Melphalan; Middle Aged; Mitoguazone; Recurrence; Salvage Therapy; Transplantation, Autologous; Vinblastine; Vinorelbine

The value of high-dose therapy with autologous stem cell transplantation as first-line therapy in poor prognosis Hodgkin's disease is controversial and we report the results of evaluation of twenty-six patients who were selected for this procedure from February 1989 to July 1994. They were all patients with stage IV at diagnosis with at least two other unfavourable characteristics, i.e. B symptoms, mediastinal mass greater than 0.45 of the thoracic diameter, two or more extranodal sites, bone marrow involvement, inguinal node involvement, serum lactic dehydrogenase greater than 400 IU/L, or low hematocrit. At the time of transplantation, 19 patients were in complete remission and 10 were in partial remission > or = 50%. Procedure-related mortality in the first 90 days post-graft was 7% overall. Of the 24 evaluable patients, 22 (92%) were assessed as complete responders, and 2 (8%) had progression of disease at 6 months. The actuarial overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) at 5 years were 69%, 79% and 58%, respectively. The Cox proportional hazards model was used to assess prognostic factors. In univariate analysis only one prognostic factor was found to be significantly associated with improved DFS, i.e. low serum lactic dehydrogenase (LDH) (DFS at 5 years: 92% if LDH < 400 IU/L vs 44% if LDH 400 IU/L, P = 0.007). DFS rates between first complete remission and first partial remission groups were not significantly different (DFS at 5 years: 87% vs 66%, p = 0.15). These first results are encouraging but randomized studies are needed.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Male; Mechlorethamine; Middle Aged; Mitoguazone; Outcome Assessment, Health Care; Prednisolone; Prednisone; Procarbazine; Prognosis; Prospective Studies; Vinblastine; Vincristine

Relapsed or refractory Hodgkin's disease (HD) patients were treated with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with hematopoietic stem cell support.. One hundred HD patients who either failed to respond to a front-line chemotherapy regimen (induction failure, n = 41) or relapsed (untreated relapse, n = 54; resistant relapse, n = 5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone 500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5, vinorelbine (Navelbine) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72 patients received HDT followed by hematopoietic stem cell support.. After MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial response, yielding an overall response rate of 75%. Patients with untreated relapse had a 92.5% response rate and those with resistant relapse or induction failure a 53% response rate. A total of 58 patients reached a CR at the end of all treatments; 12 of them relapsed. Sixty-six patients were alive with a median follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for the entire group was 59%. By univariate analysis, patients with an interval between their last treatment and salvage longer than 12 months, untreated relapse, or good performance status at salvage are shown to have longer survivals. The main toxic effects were neutropenia, thrombocytopenia, and infectious episodes. Three patients died of MINE-related complications and three after HDT.. Given early in the course of progressive HD, the MINE regimen reduced tumor burden in a high proportion of patients with relapsed or refractory disease. Responding patients further intensified with HDT have a better outcome than those who have not responded to salvage treatment.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Male; Middle Aged; Mitoguazone; Prognosis; Proportional Hazards Models; Prospective Studies; Recurrence; Salvage Therapy; Survival Rate; Treatment Failure; Treatment Outcome; Vinblastine

Fifty-four newly diagnosed patients with advanced Hodgkin's disease were randomized between two alternating non cross-resistant chemotherapies: MOPP-ABVD (MOPP: Mustine, Vincristine, Procarbazine, Prednisone-ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine) and MOPP-ABVD-CEM (CEM: Carmustine, Etoposide, methyl-GAG). There were no significant differences between the two therapies as far as complete remission, survival, relapse free survival and toxicity were concerned. This study does not support the use of MOPP-ABVD-CEM for improving the long-term outcome of patients with advanced Hodgkin's disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carmustine; Dacarbazine; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Mitoguazone; Prednisone; Procarbazine; Prospective Studies; Survival Rate; Vinblastine; Vincristine

As part of a program to develop less leukemogenic chemotherapy regimens for the treatment of favorable prognosis Hodgkin's disease, a phase I-II trial of mitoxantrone, etoposide, mitoguazone, and vinblastine was used to treat patients with relapsed and refractory malignant lymphoma and Hodgkin's disease. An overall partial response rate of 41% was observed. Although useful responses were seen, the absence of complete remissions is disappointing.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Etoposide; Hodgkin Disease; Humans; Lymphoma; Middle Aged; Mitoguazone; Mitoxantrone; Prognosis; Prospective Studies; Recurrence; Remission Induction; Vinblastine

Seventy-two patients with recurrent or refractory malignant lymphoproliferative diseases were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) and concurrent mesna to prevent urothelial toxicity; 41 patients had high/intermediate-grade non-Hodgkin's lymphoma (NHL), 18 low-grade NHL/chronic lymphocytic leukemia (CLL), and 13 Hodgkin's disease (HD). The overall response rates were 56% in high/intermediate-grade NHL, 11% in low-grade NHL/CLL, and 69% in HD respectively. Median survival in the same 3 groups was 7, 2 and 10 months respectively. Neither previous type of response to chemotherapy nor previous amount of treatment predicted the outcome of MIME chemotherapy. Toxicity was modest, hemorrhagic cystitis did not occur, and only one therapy-related death occurred. Although MIME appears to be a safe treatment with considerable activity in recurrent or refractory lymphoproliferative disease very few patients become long-term survivors. However, MIME is well suited for remission induction in patients intended for subsequent autologous bone-marrow transplantation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Hodgkin Disease; Humans; Ifosfamide; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Methotrexate; Middle Aged; Mitoguazone; Prognosis

Pulmonary Langerhans histiocytosis (PLH) is a rare disease due to the accumulation of Langerhans cells at the level of the bronchioles. These dendritic immunocytes form granulomata and destroy the wall of the airway. We report a case of PLH developing at the same time as Hodgkin's lymphoma in a young woman who smoked tobacco and cannabis. We observed a complete remission of the PLH lesions parallel to the remission of the Hodgkin's lymphoma after chemotherapy, in the absence of any change in the consumption of tobacco and cannabis. This observation leads us to discuss the potential relationships between PLH on one hand, and smoking, the lymphoma and its treatment on the other.

Topics: Accidents, Traffic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchioles; Carmustine; Cytarabine; Dacarbazine; Doxorubicin; Etoposide; Female; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Ifosfamide; Incidental Findings; Lung Diseases; Lymphatic Diseases; Marijuana Smoking; Melphalan; Methylprednisolone; Mitoguazone; Remission Induction; Smoking; Tomography, X-Ray Computed; Vinblastine; Vindesine; Vinorelbine; Young Adult

High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin's lymphoma (HL). However, the optimal salvage regimen has not yet been established.. We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy.. Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE-ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE-ESHAP (46% and 35% versus 74% and 69%, respectively).. MINE-ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cytarabine; Drug Administration Schedule; Etoposide; Female; Hodgkin Disease; Humans; Ifosfamide; Male; Middle Aged; Mitoguazone; Periodicity; Prednisone; Recurrence; Retrospective Studies; Salvage Therapy; Stem Cell Transplantation; Transplantation, Autologous; Treatment Failure; Vinblastine; Young Adult

When clinical data are subjected to statistical analysis, a common question is how to choose an appropriate significance test. Comparing two independent groups with observations measured on a continuous scale, the question is typically whether to choose the two-sample-t test or the Wilcoxon-Mann-Whitney test (WMW test). Similar results are often obtained, but which conclusion can be drawn if significance tests give highly different P-values? The t test is optimal for normally distributed observations with common variance and robust to deviations from normality if sample sizes are not very small. The WMW test makes no distributional assumptions, but depends heavily on equal shape and variance of the two distributions (homoscedasticity). We have compared the properties of the traditional two-sample t test, a modified t test allowing unequal variance, and the WMW test by stochastic simulation. All show acceptable behaviour when the two distributions have similar variance. When variances differ, the modified t test is superior to the other two.

Topics: Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Data Interpretation, Statistical; Etoposide; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Leukocyte Count; Lymphoma, Non-Hodgkin; Methotrexate; Mitoguazone; Models, Statistical; Neutrophils; Numerical Analysis, Computer-Assisted; Sample Size; Software; Statistical Distributions; Statistics, Nonparametric; Stochastic Processes; Time Factors

The MINE regimen (mitoguazone, ifosfamide, vinorelbine and etoposide) is a salvage chemotherapy for relapsed and refractory Hodgkin's disease.. We report the cases of a 16-year-old girl and a 17-year-old boy who had Hodgkin's disease and developed painful and massive subcutaneous inflammatory edema after MINE chemotherapy. Morphine was unable to control pain leading to major functional disability of joint movement. One patient had an elevated creatine kinase level, hypoalbuminemia, hypodermic and muscular edema at magnetic resonance imaging and diffuse hemorrhagic hypodermic edema at skin biopsy. The other patient was found to have only hypoalbuminemia. The clinical course was favorable in both cases within a few weeks, but with recurrent episodes of pain and localized areas of fat necrosis five months later in one case.. This side effect of MINE chemotherapy - subcutaneous inflammatory edema, myalgia and skin pain - has not been described previously for the different components of the regimen. Three clinicopathological hypotheses could be put forward: capillary leak syndrome, panniculitis, toxic fasciitis. The causal drug remains undetermined, but the most likely would be vinorelbine because of the chronology of the eruptions during the first and last days of chemotherapy and because of the known vascular toxicity of vinorelbine which could explain a capillary leak syndrome.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Capillary Leak Syndrome; Creatine Kinase; Edema; Etoposide; Fat Necrosis; Female; Hodgkin Disease; Humans; Ifosfamide; Inflammation; Magnetic Resonance Imaging; Male; Mitoguazone; Pain; Recurrence; Vinblastine

This study presents the results of a prospective study of methyl-gag, ifosfamide, methotrexate and etoposide (MIME) as salvage regimen for Hodgkin's disease (HD) in Sweden. Sixty-four patients with recurrent or refractory HD were treated with MIME between July 1988 and December 1993. All patients except one had, earlier, been treated with and failed consecutive or alternating MOPP and ABVD. Median age was 37 yr (range 14-73). Twenty patients (31%) achieved a complete remission (CR) and 17 (27%) a partial remission (PR), giving an overall response rate of 58%. The 5-yr survival for all patients was 43%. In a multivariate analysis, the most important factors predicting a poor survival were the presence of extranodal disease at relapse, male gender and high age. Twenty-nine patients were treated with high-dose chemotherapy with stem-cell rescue after MIME. Those patients had a similar survival compared to the patients responding to MIME but not treated with high-dose chemotherapy. We conclude that MIME induces remissions in a high proportion of patients with recurrent and refractory HD with acceptable toxicity. The remissions probably need consolidation, but the nature of this consolidation is still controversial.

Topics: Adolescent; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Hodgkin Disease; Humans; Ifosfamide; Male; Methotrexate; Middle Aged; Mitoguazone; Neoplasms, Second Primary; Prospective Studies; Salvage Therapy; Survival Analysis

Many centers use CY and G-CSF to mobilize PBPC. In this study we explored whether a standard chemotherapy regimen consisting of mitoguazon, ifosfamide, MTX and etoposide (MIME) combined with G-CSF was capable of mobilizing PBPC in lymphoma patients. Twelve patients with Hodgkin's disease (HD) and 38 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3 to 20) of chemotherapy prior to mobilization. It was found that the optimal time of PBPC harvest was at days 12 and 13 after initiating the mobilization regimen. The median number of collected CD34+ cells per kg body weight was 7.1 x 10(6) (range 0.5-26.2). More than 2.0 x 10(6) CD34+ cells/kg were achieved in 69% of the patients after one apheresis. When additional cycles of apheresis were done, only 6% failed to harvest this number of CD34+ cells. There was a statistically significant inverse correlation between the number of prior chemotherapy cycles and CD34+ cell yield (P = 0.003). No such association was found between CD34+ cell yield and prior radiotherapy. When MIME/G-CSF was compared with Dexa-BEAM/G-CSF, it was found that MIME/G-CSF tended to be more efficient in mobilizing PBPC in spite of being less myelotoxic. All patients transplanted with MIME/G-CSF mobilized PBPC had fast and sustained engraftment. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF can be successfully used to mobilize PBPC.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoguazone; Salvage Therapy; Time Factors

Fifty-one patients with primary refractory or relapsed malignant lymphoma (47 non-Hodgkin's lymphoma and four Hodgkin's disease) were treated with a new chemotherapeutic regimen (cisplatinum, methyl GAG, bleomocyin, methyl prednisolon). Among these 51 patients, 41 had measurable disease. Three of these 41 patients achieved complete remissions (7.3%) and 17 showed partial response (41.5%). The low hematological toxicity of this chemotherapeutic combination allowed us to give the full dose at the planned cycle date in 90% of the cycles. No major toxicity were observed (two minor neurological toxicities, one ototoxicity associated with oral mucositis toxicity, 6 febrile episodes) during 164 courses. With a median follow-up of 12 months, 18% of patients were alive without disease. We conclude that in this particular population of malignant lymphomas, Cis-BMP is an effective therapy with minimal toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cisplatin; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Mitoguazone; Prednisolone; Salvage Therapy; Survival Rate; Treatment Failure; Treatment Outcome

One hundred and three patients with recurrent or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) were retrospectively studied. Thirty-seven of the 44 patients with HD, 34/47 with high-grade malignant and 9/12 with low-grade malignant NHL were evaluable for response. Of the 37 evaluable patients with HD, 16 (43%) achieved complete remission (CR) and 4 partial remission (PR), giving a total response rate of 54%. Of the 34 evaluable patients with high-grade NHL, 5 achieved CR and 8 PR, giving a response rate of 38%. Of 9 evaluable patients with low-grade NHL, 2 achieved CR. The main toxicity was leukopenia, thrombocytopenia and infections. Twenty-six per cent of the patients developed septicaemia, which was fatal in 6 cases (6%). We conclude that MIME as salvage regimen can induce complete remissions in lymphoma patients, particularly in HD with previous heavy treatment, and that it is relatively well tolerated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Mitoguazone; Recurrence; Remission Induction; Retrospective Studies

In an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22-73), and performance status of 1 (0-3). Their diagnoses were Hodgkin's disease 5 and non-Hodgkin's lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1-5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkin's disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkin's disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Evaluation; Etoposide; Female; Hematologic Tests; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoguazone

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Etoposide; Hodgkin Disease; Humans; Ifosfamide; Methotrexate; Mitoguazone; Prognosis

Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Hematologic Diseases; Hematuria; Hodgkin Disease; Humans; Ifosfamide; Male; Methotrexate; Middle Aged; Mitoguazone

The Southwest Oncology Group has evaluated methyl-GAG on a weekly schedule among patients with lymphoma and Hodgkin's disease. Among 56 fully and partially evaluable patients responses were seen in 3 of 10 patients with Hodgkin's disease and 11 of 46 patients with lymphoma. Toxicity was acceptable. Methyl-GAG has significant antitumor activity among this group of heavily pretreated patients. Additional trials of methyl-GAG in combination with other agents are underway.

Topics: Adolescent; Adult; Aged; Drug Evaluation; Female; Guanidines; Hodgkin Disease; Humans; Lymphoma; Male; Middle Aged; Mitoguazone

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl-GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.

Topics: Adult; Aged; Bone Marrow; Digestive System; Guanidines; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Mitoguazone; Time Factors