mitoguazone and Lymphoma--Non-Hodgkin

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

Topics: Alkylating Agents; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Depsipeptides; Gallium; Humans; Lymphoma, Non-Hodgkin; Mitoguazone; Paclitaxel; Peptides, Cyclic; Suramin

To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL).. Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350 mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28-day treatment cycle.. Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis.. Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49-95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoguazone; Prednisone; Vincristine

Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoguazone; Prednisone; Survival Analysis; Treatment Outcome; Vincristine

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

The study was aimed to evaluate the effect of IEMAD (modified MIME) composed of isofosfamide, VM26 or VP16, methotrexate, cytarabine, dexamethasone or methylprednisolone, in treatment of refractory or relapsed non-Hodgkin's lymphoma. Twenty-five patients with refractory or relapsed non-Hodgkin's lymphoma (11 refractory NHL patients, 14 relapsed NHL patients) were treated with IEMAD regimen. The results showed that the complete remission rate was 24.0% (6/25) and the partial remission rate was 28.0%, having an overall response rate of 52%. The median survival duration was 13 months and the median duration of progression-free survival was 8 months. The most frequent complications were gastrointestinal complaint (nausea, vomiting etc.) and myelosuppression. No treatment related mortality was found. It is concluded that the IEMAD (modified MIME) regimen may be a safe and effective regimen that can be used in treatment of patients with refractory or relapsed non-Hodgkin's lymphoma who did not respond to other regimens.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Dexamethasone; Drug Administration Schedule; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Mitoguazone; Recurrence

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

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

To evaluate the pattern of failure and outcome of patients with aggressive non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) with an emphasis on the role of adjuvant involved-field radiotherapy (IFRT).. Fifty-three adult patients with aggressive NHL (46 intermediate-and 7 high-grade) underwent HDCT with SCR. All patients underwent induction chemotherapy prior to high dose intensification. Seven (13.2%) received IFRT to 10 disease sites either prior to or following HDCT. Indication included symptomatic or bulky disease, persistent disease, or to consolidate a complete response (CR). Sites of relapse were designated as old (involved prior to HDCT) or new (previously uninvolved). Median followup was 20.1 months (range, 1.2-69.3 months).. The 4-year actuarial progression-free (PFS) and cause-specific (CSS) survivals of the entire group were 30.0 and 50.2%, respectively. Excluding toxic deaths, 24 patients (52.2%) relapsed. Sixteen (34.7%) failed in old and 15 (32.6%) in new sites. Patients treated with IFRT had a lower rate of relapse in old sites (0 vs. 41%) (p = 0.04) than patients treated with HDCT alone. Of the 141 sites present prior to induction, 127 (90.1%) were amenable to IFRT. Excluding irradiated sites, the overall 4-year local control (LC) of all amenable sites was 61.1%. Amenable sites failing to achieve a CR to induction had a poorer LC (32.0 vs. 95.1%) (p < 0.0001) than sites in CR. The 4-year LC of sites failing to achieve a CR to HDCT was 29.4%. Adjuvant IFRT improved the 4-year LC of all sites (100 vs. 61.1%) (p = 0.05), persistent sites following induction (100 vs. 32.0%) (p = 0.01) and persistent sites following HDCT (100 vs. 29.4%) (p = 0.01). Adjuvant IFRT was not associated with any untoward acute or late toxicity.. The predominant site of relapse in patients with aggressive NHL undergoing HDCT and SCR is in sites of disease present prior to HDCT. However, the risk of relapse of prior disease sites varies greatly depending upon their response to chemotherapy. Sites at greatest risk are those failing to achieve a CR to induction regardless of their response to HDCT. IFRT is capable of reducing the high risk of relapse in these sites, the majority of which are amenable to IFRT. These results demonstrate a rationale for and possible benefit to IFRT in patients with aggressive NHL undergoing HDCT and SCR.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Dexamethasone; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Methotrexate; Methylprednisolone; Middle Aged; Mitoguazone; Radiotherapy, Adjuvant; Recurrence; Remission Induction; Treatment Failure

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Mitoguazone; Prospective Studies; Salvage Therapy; Sweden; Transplantation, Autologous; Treatment Outcome

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

Discussions from a recent cancer conference held in May of 1995 are summarized in the following areas: 1) the effect of mitoguazone in relapsed non-Hodgkin's lymphoma; 2) the addition of ddI or ddC to chemo for advanced Kaposi's sarcoma (KS); 3) progress in use of three new anti-KS agents; 4) the effectiveness of phototherapy as palliation for KS; and 5) reasons why HIV prevalence is probably underestimated in women. Additionally, the paper reviews the Lymphoma Project Report which analyzed the epidemiology, pathogenesis, diagnosis, clinical manifestations, molecular characteristics, prognostic factors, and treatment of AIDS lymphoma. The following were among the findings: a regimen of doxorubicin, bleomycin, and vincristine with either ddI or ddC was well tolerated and evoked antitumor responses in patients with KS; 9-cis-retinoic acid and beta-human chorionic gonadotropin can induce remission of KS lesions; photodynamic therapy is an effective palliative therapy for some people with KS, but doses above 300 joules/cm2 result in scarring; and most American women who die of cervical cancer probably also have HIV infection according to a clinician from State University of New York in Brooklyn. The article concludes with a discussion of the differences between the focus of HIV research and HIV meetings for the ASCO assembly and the AIDS community.

Topics: Acquired Immunodeficiency Syndrome; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Chorionic Gonadotropin; Female; Humans; Isotretinoin; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Mitoguazone; Paclitaxel; Palliative Care; Photochemotherapy; Recurrence; Sarcoma, Kaposi; Uterine Cervical Neoplasms

Two studies of mitoguazone (MGBG) have led researchers to believe the drug would be effective in the treatment of newly-diagnosed AIDS lymphoma, especially lymphoma of the central nervous system. ILEX, MGBS's developer, can help people who qualify for new trials but are unable to get to one of the twenty-nine trial centers with expenses. Those who do not qualify for the trials may be eligible to receive the drug on a compassionate-use basis.

Topics: Acquired Immunodeficiency Syndrome; Antineoplastic Agents; Central Nervous System Neoplasms; Clinical Trials as Topic; Humans; Lymphoma, Non-Hodgkin; Mitoguazone; Treatment Failure

The first results of the management of adult non-Hodgkin lymphoma according to the National Protocol are reported. 164 pts (71 female and 93 male), aged 50 (range 15 to 79 years) were included. 89 pts had lymphomas with intermediate, 34 with low and 24 with high grade malignancy. 65% had advanced stages (III and IV). In the low grade malignancy group 38% were in complete remission and actuarial survival at 20 months was 80%. In the intermediate grade group, stages I and II the corresponding values were 79 and 85%; in the intermediate grade stages III and IV, 58 and 69%, and in the high grade group 61 and 77%. Bone marrow toxicity and infections were the main complications. 32 pts have died, 10 of them with drug toxicity complications.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Ifosfamide; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Mitoguazone; Neoplasm Staging; Prednisone; Procarbazine; Vincristine

The involvement of mitochondrial damage in the antiproliferative effects of m-iodobenzylguanidine [MIBG] and methylglyoxal bis (guanylhydrazone) [methylGAG] was studied in human neuroblastoma SK-N-SH, mouse neuroblastoma N1E115 and mouse lymphosarcoma S49 cells. Proliferation of SK-N-SH cells was insensitive to MIBG (100 microM gave 15% inhibition), but sensitive to methylGAG (IC50 = 50 microM). MIBG and methylGAG were approximately equitoxic to N1E115 cells (IC50 of 92 and 87 microM, respectively). S49 cells were most sensitive to both MIBG (IC50 = 11 microM) and methylGAG (IC50 = 5 microM). In isolated sonicated mitochondria, MIBG inhibited respiration a complex I of the respiratory chain (EC50 = 0.5 mM), whereas methylGAG was much less effective (EC50 greater than 15 mM). In intact cells, MIBG at 31 microM impaired mitochondrial respiration and stimulated the glycolytic flux. In contrast, equimolar concentrations of methylGAG had no effect on oxygen consumption, ATP content, glucose consumption and lactate production. MethylGAG significantly increased putrescine levels in N1E115 and S49 cells within 12 hr via inhibition of S-adenosylmethionine decarboxylase. No such effects were seen in SK-N-SH cells for up to 48 hr. Equimolar concentrations of MIBG had no effect on the putrescine levels in the various cell lines, suggesting that MIBG did not inhibit S-adenosylmethionine decarboxylase. It is concluded that the antiproliferative mechanisms of the guanidino compounds are essentially different. MIBG inhibited mitochondrial respiration at complex I with concomitant stimulation of the glycolytic flux but was essentially without effect on polyamine levels. On the other hand, cytotoxicity of methylGAG was not associated with mitochondrial dysfunction.

Topics: 3-Iodobenzylguanidine; Animals; Antineoplastic Agents; Cell Division; Cell Survival; Humans; Intracellular Fluid; Iodobenzenes; Lymphoma, Non-Hodgkin; Mitochondria; Mitoguazone; Neuroblastoma; Polyamines; Tumor Cells, Cultured

With the intent of using active regimens in the front-line setting, new combinations of chemotherapy have been tested as salvage treatment in lymphoma patients at M.D. Anderson Hospital. Combinations based on ifosfamide plus etoposide, including IMVP-16 (ifosfamide/methotrexate/etoposide) and MIME (methyl-GAG/ifosfamide/methotrexate/etoposide) resulted in overall and complete responses (CRs) of 60 and 25%, respectively. Long-term follow-up of MIME indicates a 25% cure rate in intermediate-grade lymphoma patients who achieve CR. The in vitro synergism of platinum and high-dose cytarabine recently has been confirmed clinically. A study is currently under way to evaluate the effect of integrating MINE (mesna/ifosfamide/mitoxantrone/etoposide) and ESHAP (etoposide/methyl prednisolone/cytarabine/platinum) into one protocol.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Drug Evaluation; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Lymphoma; Lymphoma, Non-Hodgkin; Mesna; Methotrexate; Methylprednisolone; Methylprednisolone Hemisuccinate; Mitoguazone; Mitoxantrone; Remission Induction; Survival Rate

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

The authors report the results of a chemotherapy regimen of methyl-GAG, etoposide and prednimustine in 21 elderly patients (median age = 78 years) with aggressive non-Hodgkin's lymphoma. Sixteen patients responded (11 complete remissions, 5 partial remissions) with minor toxic side-effects. This regimen could be proposed for patients whose age and/or cardiovascular status prohibit treatment with usual anthracycline-containing chemotherapy programs.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mitoguazone; Prednimustine; Survival Rate

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

It was shown in experiments with Pliss' lymphosarcoma in rats that antifolates--cis-2,5-bis (aminohydroxymethyl)-piperazine-3,6-dione and methotrexate--cause tumor cell spermidine level to drop. Also, treatment with antifolates prevented the undesirable accumulation of S-adenosylmethionine in tumor cells induced by methyl-glyoxal-bis (guanylhydrazone) which inhibits polyamine biosynthesis. In chemotherapeutic experiments with rat lymphosarcoma, antifolates markedly potentiated the antitumor effect of methylglyoxal-bis (guanylhydrazone). The data suggest that the combination of polyamine biosynthesis inhibitors such as methylglyoxal-bis (guanylhydrazone) and alpha-difluoromethylornithine and antifolates may be useful in tumor chemotherapy.

Topics: Adenosylmethionine Decarboxylase; Animals; Cycloserine; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Folic Acid Antagonists; Lymphoma, Non-Hodgkin; Male; Methotrexate; Mitoguazone; Neoplasm Transplantation; Polyamines; Rats; S-Adenosylhomocysteine; Time Factors

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Etoposide; Hematologic Diseases; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Mitoguazone