mesna and Lymphoma--Non-Hodgkin

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Cisplatin; Cytarabine; Etoposide; Humans; Ifosfamide; L-Lactate Dehydrogenase; Lymphoma, Non-Hodgkin; Mesna; Methylprednisolone; Middle Aged; Mitoxantrone; Outcome Assessment, Health Care; Prognosis

Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.. Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast cancer. Mesna (360 mg/m2) or saline administration occurred 15 minutes prior and three hours post doxorubicin. Pre-treatment and post-treatment measurements of oxidative stress, TNF-α and related cytokines were evaluated during the two experimental cycles of chemotherapy.. Co-administration of mesna with chemotherapy reduced post-treatment levels of TNF-related cytokines and TNF-receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2) (p = 0.05 and p = 0.002, respectively). Patients with the highest pre-treatment levels of each cytokine and its receptors were the most likely to benefit from mesna co-administration.. The extracellular anti-oxidant mesna, when co-administered during a single cycle of doxorubicin, reduced levels of TNF-α and its receptors after that cycle of therapy, demonstrating for the first time a clinical interaction between mesna and doxorubicin, drugs often coincidentally co-administered in multi-agent regimens. These findings support further investigation to determine whether rationally-timed mesna co-administration with redox active chemotherapy may prevent or reduce the cascade of events that lead to CICI.. clinicaltrials.gov NCT01205503.

Topics: Antineoplastic Agents; Breast Neoplasms; Cognition Disorders; Cross-Over Studies; Doxorubicin; Drug Interactions; Female; Humans; Interleukin-18; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Oxidation-Reduction; Protective Agents; Receptors, Tumor Necrosis Factor; Solubility; Tumor Necrosis Factor-alpha

In aggressive non-Hodgkin lymphoma (NHL), CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone) regimen has been standard for decades, and rituximab has increased response rates and survival in CD20 positive patients, recently. The aim of this prospective trial was to evaluate the long-term efficacy and toxicity of MINE as a consolidation treatment in aggressive NHL patients who had achieved CR or unproven CR after six cycles of CHOP in the first line setting. The primary end-point was disease-free-survival (DFS). Thirty-eight patients were enrolled between February 1992 and May 2000. All of the patients received two cycles of MINE (mesna 1.3 g/m(2), ifosfamide 1.3 g/m(2), etoposide 65 mg/m(2) on days 1-3, and mitoxantrone 12 mg/m(2) on day 1, every 3 weeks) following response to CHOP. Initial bulky disease sites were also applied radiotherapy. Male/female ratio was 1.53(23/15). Median age was 49(30-73). Most of the patients had advanced stage (84.2% for stage >3) and high IPI score (79% for IPI score >2). Sixty percent had diffuse large cell histology. Median follow-up time was 118 months (9-195). Actual mean dose intensity was 88%. There were seven febrile neutropenia episodes. Two patients had grade two neuropathy, one had grade three mucositis and another one had non-neutropenic pneumonia. There was no early toxic death. No serious late toxicity was observed during long-term follow-up. Five- and 10-year DFS rates were both 65.3%. DFS rate in the patients with more than two poor prognostic factors according to IPI score is remarkably high (88%). Five- and 10-year OS was 62.5 and 59%, respectively. MINE regimen seems to be effective as a consolidation regimen, especially, in intermediate/high risk patients and has low early and late toxicities, and it warrants to be evaluated in phase III randomised trials with rituximab in CD20 positive aggressive NHL patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Fever; Follow-Up Studies; Humans; Ifosfamide; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Peripheral Nervous System Diseases; Prednisolone; Prospective Studies; Radiotherapy, Adjuvant; Remission Induction; Treatment Outcome; Vincristine

The prognosis in patients with primary refractory or relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year survival being generally reported at 10%.. Multiple salvage regimens have been investigated and, while response rates of 50-80% have been noted in selected patients, the long-term prognosis remains poor. Following the encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in patients with primary refractory or relapsed high grade NHL.. The regimens were modified by a reduction in the intensity of intrathecal therapy. It was planned to mobilize peripheral blood stem cells following the IVAC cycle for use in subsequent autologous peripheral blood stem cell transplantation in chemosensitive patients. The initial plan was to recruit 50 patients, but the study was closed after 8 due to excessive toxicity.. We conclude that the CODOX-M/IVAC regimen is too toxic for this group of patients and does not result in better response rates than those to currently available salvage regimens.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease Progression; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Ifosfamide; Injections, Spinal; Lenograstim; Leucovorin; Lymphoma, Non-Hodgkin; Male; Mesna; Methotrexate; Middle Aged; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Prognosis; Recombinant Proteins; Salvage Therapy; Sepsis; Treatment Outcome; Vincristine

Treatment with the anti-CD20 antibody rituximab prior to stem cell collection may lead to tumor-free stem cell collections in patients with B-cell lymphoma undergoing autologous stem cell transplantation. To test the feasibility of obtaining polymerase chain reaction (PCR)-negative stem cell collection, 30 patients with a variety of B-cell lymphomas were enrolled in a protocol employing a common MINE (mitoxantrone/ifosfamide/etoposide) salvage regimen with rituximab (in vivo purging). Rituximab 400 mg/m2 was administered weekly for 3 weeks on days 1, 6, and 8 in relation to the last MINE cycle, which was followed by growth factor-stimulated peripheral stem cell collection. The median number of CD34(+) cells/kg was 2.5 million cells/kg collected over a median of 5 days. Polymerase chain reaction amplification for the t (14;18) or the heavy-chain gene rearrangement was performed prior to treatment and on the leukapheresis sample. Out of 15 patients who had a positive PCR signal prior to treatment, 10 had PCR-negative stem cell collections, whereas 5 had PCR-positive stem cell collections. After high-dose chemotherapy and stem cell transplant, all patients with a PCR-positive signal pretreatment became PCR negative. We conclude that rituximab may increase the yield of tumor-free stem cells. Higher rates of PCR negativity have been reported when more intense and protracted chemoimmunotherapy regimens have been employed. The magnitude of clinical benefit and the significance of the PCR analysis in stem cells after rituximab requires larger studies.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Etoposide; Female; Humans; Ifosfamide; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Polymerase Chain Reaction; Recurrence; Remission Induction; Rituximab; Salvage Therapy; Stem Cells; Time Factors

To analyze the results with involved-field radiotherapy after aggressive lymphomas had decreased in size by 50-99% in response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy.. From 1988 through 1996, 294 previously untreated patients with Working Formulation intermediate-grade or large-cell immunoblastic lymphomas underwent CHOP-based chemotherapy on 2 consecutive protocols at the M. D. Anderson Cancer Center. Forty-four (15%) of these patients achieved, based on international working group guidelines, a partial (50-75%) response (n = 25), or unconfirmed complete (76-99%) response (n = 19) to a median of 6 cycles of chemotherapy. These patients were treated with salvage involved-field radiotherapy (n = 32) or chemotherapy (n = 12), e.g., MINE-ESHAP, without autologous stem-cell rescue (ASCR).. Median follow-up was 43 months. Partial responders experienced similar outcomes to unconfirmed complete responders. Local control (4-year rates: 86% vs. 53%, p = 0.009) and progression-free survival (4-year rates: 67% vs. 8%, p < 0.0001), but not overall survival (4-year rates: 70% vs. 50%, p = 0.067) were significantly better in those who received salvage radiotherapy, which was well tolerated.. Progression-free and overall survival in aggressive lymphoma patients who underwent salvage radiotherapy were similar to results reported for high-dose chemotherapy with ASCR. The role of salvage radiotherapy in partial and unconfirmed complete responders to CHOP chemotherapy justifies examination in a large, cooperative group trial.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Etoposide; Humans; Ifosfamide; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin; Mesna; Methylprednisolone Hemisuccinate; Middle Aged; Mitoxantrone; Prednisone; Retrospective Studies; Salvage Therapy; Vincristine

Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL).. Thirty-eight patients with relapsed/refractory NHL who had been exposed to doxorubicin as well as the cytarabine-cisplatin combinations received Mesna 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour; ifosfamide 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour (same bag); Novantrone 8 mg/M2/D i.v. day 1; and Taxol 27.5 mg/M2/D daily days 1, 2, 3, 4 by continuous 24-hour intravenous infusion. Premedication for Taxol included dexamethasone, diphenhydramine, and cimetidine on day 1.. Of 35 evaluable patients, 9 (26%) achieved a complete response and 7 (20%) a partial response for a total response rate of 46%. The median failure-free and overall survival times were 2 and 10 months, respectively. Major toxicity was hematologic with a median absolute neutrophil nadir of 196/mm3. Only 10% of the cycles were associated with a grade 3-4 infection.. MINT is an active and safe regimen for relapsed/refractory NHL that have failed both an Adriamycin-containing regimen and a cytarabine/cisplatin-containing regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Paclitaxel; Recurrence; Taxoids; Time Factors; Treatment Outcome

CHOP is currently considered the gold standard of treatment for intermediate grade lymphomas. We designed a new regimen known as 'ATT' (alternating triple therapy) which uses three non-cross resistant combinations in alternating sequence for nine cycles.. This is a phase II clinical trial with comparison to CHOP/CMED historical controls using prognostic factors. The tumor score system was used to evaluate the results of this trial. Two hundred sixty-eight eligible patients who had one or more of the following adverse features: bulky disease, elevated LDH or > 1 extranodal site were analyzed. Outcome measures consist of survival and failure free survival.. At a median follow-up of 32 months, there was no statistically significant difference in survival for those with favorable prognostic factors (tumor score < or = 2). However, there was a statistically significant difference in favor of ATT for those with unfavorable tumor scores. When we examined the failure-free survival of those with unfavorable tumor scores, we again observed a superiority for the ATT regimen over CHOP/CMED but the opposite was true for those with favorable tumor scores. We also found a statistically significant difference in favor of the ATT regimen when compared with CHOP/CMED for patients < or = 60 years old with a tumor score > or = 3, while no advantage was found for those > 60 years.. ATT appears more effective but only for patients < 60 years old with unfavorable tumor scores. In those older than 60 years with favorable tumor score, CHOP/CMED appears superior. ATT might be an adequate regimen for young patients with poor prognostic features while CHOP/CMED might be a better choice for those with good prognosis irrespective of age. For those > 60 years with unfavorable tumor scores neither ATT or CHOP/CMED were adequate treatment. Because of the phase II nature of this study, these conclusions should be considered as hypotheses which require prospective testing.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin; Male; Mesna; Methotrexate; Methylprednisolone Hemisuccinate; Middle Aged; Mitoxantrone; Prednisone; Prognosis; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Prospective Studies; Treatment Outcome

Treatment of Hodgkin's disease (HD) and non-Hodgkin lymphomas (NHL) is still unsatisfactory in patients resistant to primary therapy or those with early relapses. The objective of the trial was to test whether salvage regimens based on a combination of iphosphamide and etopozide have a sufficient anti-lymphoma effect, while the toxicity is still acceptable, and in conjunction with growth factors as satisfactory mobilizing potential for the collection of peripheral stem cells (PBSC).. A group of 40 patients with relapsing and/or primary therapy resisting lymphomas (14 NHL, 26 HD) were treated by life saving or stimulating chemotherapy VIM (etopozide, iphosphamide, methotrexate) and MINE (iphosphamide mitoxanthrone, etopozide; mostly NHL). If the response to these regimes was inadequate, to some patients in addition mini (dexa) regimes were administered, BEAM and DHAP resp., with the objective to achieve maximum reduction of the tumourous mass before high-dosage treatment with the support of autologous PBSC. The authors administered 119 cycles of salvage chemotherapy (51 VIM, 46 MINE, 22 mini-dexa-BEAM and DHAP). The toxicity of chemotherapy and the therapeutic response were evaluated according to WHO criteria. The toxicity of VIM and MINE, with the exception for mobilization of desirable transient leukopenia, was not serious. During stimulation of PBSC on average three leukophereses were made and on average 9.9. 10(6) CD34+ cells/kg body weight of the patient were obtained and 53.2. 10(4) CFU-GM/kg (VIM), and 13.5. 10(6) CD34+ cells/kg 53.4. 10(4) CFU-GM/kg (MINE) resp. A total of 64% (MINE) and 61% (VIM) therapeutic responses were obtained, 14% (MINE) and 26% (VIM) complete remissions and 50% (MINE) and 35% (VIM) partial remissions.. Life saving regimes, VIM and MINE, have a good antilymphoma activity, low toxicity and in combination with growth factors (filgrastim) they ensure a good collection of PBSC. As compared with other regimens, in particular for stimulation, VIM and MINE appear to be better.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Leukapheresis; Lymphoma, Non-Hodgkin; Male; Mesna; Methotrexate; Middle Aged; Mitoxantrone; Recurrence; Salvage Therapy; Transplantation Conditioning

A prospective phase II study was carried out in 48 patients with relapsed or refractory non-Hodgkin's lymphoma using paclitaxel 27.5 mg/M2 i.v. by continuous infusion over 24 hours daily on days 1, 2, 3, and 4 in combination with mitoxantrone 8 mg/M2 i.v. on day 1 and ifosfamide/mesna 1.33 grams/M2 i.v. daily on days 1, 2, and 3 (MINT). Responding patients completed four cycles of MINT and were consolidated with etoposide, solumedrol [methylprednisolone], high-dose cytarabine [Ara-C], and platinum (ESHAP). Forty-eight patients were entered in the study between 1994 and 1996 at The University of Texas M. D. Anderson Cancer Center. Overall response after the first four cycles of MINT was 67% (16% complete response [CR]+ 51% partial response [PR]) and after consolidation with ESHAP it was 49% (26% CR + 23% PR). Variables associated with an improved CR rate and better failure-free survival included the number of prior treatments and the response to prior treatment. A comparison with a similar group of patients treated with mesna, ifosfamide, mitoxantrone, and etoposide (MINE)-ESHAP revealed no major differences in outcome.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Disease-Free Survival; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Methylprednisolone; Middle Aged; Mitoxantrone; Paclitaxel; Prospective Studies; Recurrence; Remission Induction; Survival Rate; Treatment Outcome

To evaluate the effect of two filgrastim dosages after autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL).. Eighty-six patients were enrolled onto a multicenter, randomized, open-label study. The study compared the efficacy and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on day 1 following ABMT.. Both patient groups were well matched in terms of demography and disease. The results showed no statistical difference in the median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11 days; P = .685) and no difference in the median duration of neutropenia (10 v 11 days, respectively; P = .567) between either dose of filgrastim. The incidence and duration of fever and neutropenic fever were the same in both groups. The number and mean duration of clinically and documented infections, duration of intravenous (IV) antibiotics, time to discharge from hospital, and tumor response also were similar in both groups.. This study demonstrates that a dose of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a similar efficacy and safety profile compared with the 10-microgram/kg/d dose administered as a SC continuous infusion. The lower dose of filgrastim has potential cost-saving implications in terms of both the dose of drug administered and the ease of administration. Based on these findings, the recommended dose of filgrastim after ABMT should be 5 micrograms/kg/d.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Mesna; Middle Aged; Neutropenia; Patient Selection; Recombinant Proteins; Thiotepa

In this study, 54 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated in a phase II, multicentric trial with ifosfamide-mesna 1500 mg/m2 IV days 1-3, idarubicin 12 mg/m2 IV day 1 and etoposide 100 mg/m2 IV day 1-3 (MIZE). Overall response was 72%; complete response (CR) and partial response (PR) were 46% and 26% respectively. In Stage I-II pts CR was 59% and in Stage III-IV pts CR was 40.5%. Patients who relapsed from an initial CR had a 64% CR rate when treated with MIZE, in contrast to refractory disease's patients who only had 19% CR (p = 0.004). The group of pts that had an objective response (CR + PR) to front line therapy had a 2 year survival rate of 55% compared with none for refractory disease (p = 0.029) after salvage therapy. Median survival for the entire group was 17.5 months. Better survival was seen in pts who were asymptomatic with low levels of LDH, previous CR, non high-grade histology, and limited disease stage at relapse. Toxicity was mainly hematologic: 91.5% had neutropenia, (56.5% grade III-IV), and 9.5% died from infectious complications. Other clinical toxicities including cardiac toxicity were negligible. MIZE chemotherapy was effective in patients with relapsed and refractory lymphoma and showed limited clinical and cardiac toxicity. Myelosupression was the most frequent single toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Humans; Idarubicin; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Recurrence; Salvage Therapy

This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals.. We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively.. Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths.. CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Epirubicin; Etoposide; Feasibility Studies; Female; Folic Acid; Hematologic Diseases; Humans; Ifosfamide; Karnofsky Performance Status; Lymphoma, Non-Hodgkin; Male; Mesna; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Staging; Prednisolone; Remission Induction; Risk Factors; Survival Rate; Vincristine

High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin's lymphoma who have relapses. In this report we describe a prospective randomized study of such treatment.. A total of 215 patients with relapses of non-Hodgkin's lymphoma were treated between July 1987 and June 1994. All patients received two courses of conventional chemotherapy. The 109 patients who had a response to chemotherapy were randomly assigned to receive four courses of chemotherapy plus radiotherapy (54 patients) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation (55 patients).. The overall rate of response to conventional chemotherapy was 58 percent; among patients with relapses after chemotherapy, the response rate was 64 percent, and among those with relapses during chemotherapy, the response rate was 21 percent. There were three deaths from toxic effects among the patients in the transplantation group, and none among those in the group receiving chemotherapy without transplantation. The two groups did not differ in terms of prognostic factors. The median follow-up time was 63 months. The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation. At five years, the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation (P = 0.001), and the rate of overall survival was 53 and 32 percent, respectively (P = 0.038).. As compared with conventional chemotherapy, treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin's lymphoma in relapse.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Prospective Studies; Recurrence; Salvage Therapy; Survival Analysis; Transplantation, Homologous

Ifosfamide (2.0 g/m2 intravenously/day x 3) with mesna (400 mg/m2 intravenously q 4 h daily x 3) was combined with mitoxantrone (14 mg/m2 intravenously x 1) and given on a 3 week schedule to patients with previously treated non-Hodgkin's lymphoma. In 45 eligible/evaluable patients, a 47% response rate (95% confidence interval: 32%, 62%) was achieved of which 25% were complete responses and 22% were partial responses. Median duration of remission was 10 months with 42% of patients in remission at 18 months. Hematologic toxicity (granulocytopenia) was the dose-limiting toxicity with severe or life-threatening granulocytopenia in 98% of patients at full protocol doses. Nausea/vomiting was seen in 73% of patients but was usually mild/moderate. Three patients had significant hematuria secondary to ifosfamide. Two patients had severe changes in the left ventricular ejection fraction (LVEF) secondary to mitoxantrone; and one patient had acute neurologic dysfunction secondary to ifosfamide. Ifosfamide/mesna can be safely combined with mitoxantrone at full doses in previously treated patients with non-Hodgkin's lymphoma. This combination should be considered for other trials in lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Remission Induction; Survival Rate

In a prospective multicenter therapy trial the remission-inducing potential of the COP-BLAM (5 courses) and the possibly not cross-resistant IMVP-16 (2 courses) regimen for advanced diffuse large cell lymphomas were investigated. Inadequately responding patients were switched early after 2-3 courses to the IMVP-16 protocol. Between January 1986 and August 1988 349 previously untreated patients were recruited who fulfilled the entry criteria: age 15-75 (mean 56 years), stage II-IV. A first restaging after 3 courses of chemotherapy was documented for 280 cases, a second restaging following 7 courses of chemotherapy or a final report was available for 221 patients, 130 of which where in CR (59%). These figures include 29 cases who died already during induction-chemotherapy of progressive disease (n = 17) as well as of therapy-related complications in CR (n = 12). Thirty-three patients were switched early to IMVP-16 due to incomplete response at the first restaging; 13 of those achieved CR by the new regimen (39%), 9 achieved a partial remission which was turned into CR by additional radiotherapy in 5 cases. Dose reductions and interval prolongations were necessary at increasing rates with subsequent chemotherapy courses (20-50% of the cycles). Relapses have occurred in 32 patients so far (14 early, 18 after stop of treatment). The median survival was 24 months (n = 309 patients). These data show that this treatment strategy is effective in a large unselected group of patients of relatively high age. However, patients showing only delayed response with this protocol probably need more aggressive regimens to obtain durable remissions.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Mesna; Methotrexate; Middle Aged; Prednisone; Procarbazine; Prospective Studies; Risk Factors; Vincristine

In a multicenter prospective randomized therapeutic trial in advanced (stage II-IV disease, Ann Arbor classification) high-grade malignant non-Hodgkin's lymphomas (NHL, Kiel classification) a sequential combination of the COP-BLAM (5 cycles) and the IMVP-16 (2 cycles) protocols was employed. Response was first determined after 2-3 cycles. In a response-adapted manner the therapy was immediately switched to IMVP-16 if only a partial remission or no response was obtained as evidenced by the first restaging. The aim of the study is the investigation of the efficiency of this concept to induce stable remissions. In an additional randomized trial, involving all patients reaching complete remissions after chemotherapy (second restaging), the prognostic relevance of adjuvant radiotherapy as compared to therapy-free follow-up is evaluated. Eighty percent of the 191 recruited qualified patients have so far become evaluable. Complete clinical remissions were achieved in 76/148 (51%) of the patients up to the first, in 52/85 (61%) of the patients up to the second restaging. Only in a few cases did the expected toxicity of intensive polychemotherapy reach WHO grade 3-4, including nausea and diarrhea, infections, septic complications, myelotoxicity, and stomatitis. Four of the 29 deaths recorded so far occurred in complete remission due to treatment-related complications, whereas 22/29 (76%) died in progression and 3 of unrelated causes.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Mesna; Methotrexate; Prednisone; Procarbazine; Vincristine

Various malignancies and cytotoxic chemotherapy have been proposed to increase the risk of reactivation of tuberculosis. Available literature to support this observation is still conflicting. There is scarcity of data from countries with rampant tubercular infection, such as India, in this regard.. In the present retrospective analysis, patients with high-grade non-Hodgkin's lymphoma with past history of tuberculosis and have had adequate antitubercular therapy were identified from a Lymphoma Group study. These patients were followed up during cytotoxic chemotherapy and later to assess the risk of reactivation.. A cohort of eight patients with past history of tuberculosis was selected from 141 patients of high-grade non-Hodgkin's lymphoma. The median age was 33.5 years (range, 24-53 years). Median duration between completion of antitubercular treatment and diagnosis of lymphoma was 5 years (range, 1.5-10 years). All patients received cyclical cytotoxic chemotherapy. The median duration of follow up after completion of chemotherapy was 5 years (range, 10 months to 5 years). None of these patients developed reactivation of tuberculosis.. Cyclical chemotherapy for non-Hodgkin's lymphoma does not lead to reactivation of tuberculosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Methylprednisolone; Middle Aged; Mitoxantrone; Mycobacterium tuberculosis; Prednisone; Retrospective Studies; Tuberculosis; Vincristine; Virus Activation

Non-Hodgkin lymphomas (NHL) in children are the second most common malignant tumors in Kuwait. Until 1995 the patients (pts) received institutional protocols. From October 1995 to September 2000 21 children with NHL were treated. Five children were treated by NHL BFM 90 protocol, 7 pts received NHL BFM 95 scheme, and 9 children underwent therapy abroad or according to different types of protocols. The results of a retrospective analysis of NHL BFM 95 protocol in Kuwait are reported. Seven patients diagnosed with NHL--group B: 3 children with Burkitt lymphoma (B-cell NHL) and group A: 4 children with lymphoblastic lymphoma (T-cell NHL)--were treated from October 1995 to September 2000 in the Kuwait Cancer Control Centre according to NHL BFM 95 protocol. Group B consisted of 2 girls and 1 boy; median age at diagnosis was 4 years 8 months, 2 pts classified as stage II and 1 pt as stage III. All patients were assigned to risk group R2. Median follow-up is 2 years 8 months. Group A included 1 girl and 3 boys; median age at diagnosis was 5 years 8 months, 1 pt classified as stage III and 3 pts as stage IV. All patients were assigned to IR group. Median follow-up is 3 years 6 months. In group B all 3 pts are in 1st CR; in group A 3 pts are in 1st CR and 1 pt having Li-Fraumani syndrome died after the 3rd relapse of disease during therapy. In both groups there was no toxic death, myelotoxicity WHO grade III-IV, hepatotoxicity WHO grade II-III. Treatment results of NHL BFM 95 study in our small group of patients are very optimistic. Six patients are in 1st CR and one died due to progression of disease. Despite the small group of patients, the results suggest that NHL BFM 95 protocol is highly effective and safe with regular supportive care.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Burkitt Lymphoma; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Infant; Kuwait; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Mercaptopurine; Mesna; Methotrexate; Neoplasm Staging; Prednisolone; Prednisone; Survival Rate; Thioguanine; Treatment Outcome; Vincristine

Alkylating drugs (cyclophosphamide and ifosfamide) have been in clinical use for the treatment of malignant diseases in the past. They are most useful anticancer agents and cyclophosphamide is also widely used for its immunosuppressive properties. However the effect of alkylating drugs on thyroid hormone parameters have not been evaluated so far. Three groups of patients were prospectively evaluated: Group I: 15 patients with Wegener's granulomatosis and 4 patients with severe scleritis received a single dose cyclophosphamide (15 mg/kg bw/day) and 250 mg prednisone i.v. Group II: 9 patients with malignant lymphomas were treated according to the IMVP 16-protocol. Patients received daily ifosfamide 1000 mg/m2 from day 0 to 4 and vepesid from day 0 to 2. Patients did not receive corticosteroids additionally. Group III: 6 patients with a relapse of malignant lymphomas received ifosfamide 1.500 mg/m2/day from day 0 to 4 i.v. and dexamethasone 40 mg/m2 as well as ara-c and etoposid. All patients received mesna to prevent hemorrhagic cystitis and odansetran or metoclopramide as antiemetic drugs. Alkylating drugs were given as a one hour infusion. Thyroid hormone parameters were determined before and on day 1, 2, 3, 4 after drug administration. We observed a significant increase in T4 and fT4 concentrations and a concomitant fall in TSH in either group one day after the administration of alkylating drugs. The effect was most pronounced in group III: T4 increased from 113 +/- 8 nmol/L to 175 +/- 8 (normal: 58-154) and fT4 from 14.0 +/- 0.8 to 24.8 +/- 2.5 pmol/L (normal 10-25). TSH dropped from 1.27 +/- 0.16 to 0.33 +/- 0.07 mU/L (normal 0.3-4). All changes were significant: p < 0.001. Two of the six patients displayed biochemical hyperthyroidism. Also reverse T3 increased significantly. Two days after drug administration a gradual normalization occurred. However, T3, Tg, TBG, Transthyretin and albumin levels did not change throughout the study period. One patient with coexisting hypothyroidism, who received his last thyroxine substitution therapy one day before the administration of cyclophosphamide (as in group I), also demonstrated an increase in T4, fT4 and rT3 and a fall in TSH concentrations. I.v. administrations of cyclophosphamide and ifosfamide induce a transient increase in T4 and fT4 concentrations and a concomitant fall of TSH in the presence of normal Tg, T3 and thyroid binding protein concentrations. These data suggest, that the changes are not due t

Topics: Adult; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dexamethasone; Granulomatosis with Polyangiitis; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Mesna; Middle Aged; Prednisone; Recurrence; Scleritis; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Platinum-based regimens have been the most commonly used salvage therapy for non-Hodgkin's lymphoma (NHL). In this update of two of these regimens with long-term follow-up data, we provide evidence that the etoposide-containing regimen (ESHAP) is superior to a cisplatin-cytosine arabinoside-based regimen (DHAP) in response rate, survival, and time to treatment failure. In spite of this superiority, the long-term outcome for most patients with relapsed or refractory NHL remains unfavorable. Newer salvage regimens such as MINE-ESHAP, or, when feasible, high-dose chemotherapy with transplant, are probably better choices than either DHAP or ESHAP alone.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Dexamethasone; Disease-Free Survival; Etoposide; Follow-Up Studies; Humans; Ifosfamide; Life Tables; Lymphoma, Non-Hodgkin; Mesna; Methylprednisolone; Methylprednisolone Hemisuccinate; Mitoxantrone; Prognosis; Salvage Therapy; Texas; Treatment Outcome

In recent years, more effective and less toxic treatment protocols have been developed to increase the cure rates in intermediate and high grade non-Hodgkin's lymphoma (NHL). This study was undertaken to investigate the efficacy and toxicity of MINE (ifosfamide, mesna, mitoxantrone and etoposide) combination chemotherapy in patients with intermediate and high grade NHL. Twenty-one patients (16 male, 5 female; age between 26 and 70 years) with NHL were included in the study. An overall response rate of 73% and complete response rate of 56% were achieved and survival rate for responding patients was 80% at the 48th month. Side effects including mild myelosuppression, nausea/vomiting and alopecia were observed. MINE combination seems to be effective and well tolerated without significant toxicity as a first-line therapy in patients with intermediate or high grade NHL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Remission Induction; Survival Rate; Treatment Outcome

Twenty-one consecutive patients with refractory or relapsed non-Hodgkin's lymphomas were treated with a novel combination chemotherapy (MINE-BOP), comprising myelosuppressive (ifosfamide, mitoxantrone, etoposide) and non-myelosuppressive (bleomycin, vincristine and prednisone) drugs. Median age of the patients was 42 years and all had intermediate or high-grade lymphoma. Fifteen patients had refractory disease. All patients had previously been treated with one or two regimens, containing anthracyclines. In all cases the duration between the last chemotherapy and the MINE-BOP regimen was shorter than 12 months. Response rate was 57% with 33% complete remission (CR). Median disease-free and overall survivals were 7 and 10 months respectively. The serum LDH level was the only significant prognostic factor in this study. The toxicity of this regimen was moderate with 24% of febrile neutropenia and 9% of microscopic hematuria. Toxic death due to febrile neutropenia was observed in one patient who had bone marrow involvement. To conclude, the addition of non-myelosuppressive drugs to the chemotherapy regimen and shortening the interval between the application of cytotoxic drugs as used in the present study did not show any improvement of response and survival in this group of patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematuria; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Mitoxantrone; Neutropenia; Prednisone; Prospective Studies; Recurrence; Survival Rate; Vincristine

Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Busulfan; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukapheresis; Lymphocyte Count; Lymphocyte Subsets; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Melphalan; Mesna; Middle Aged; Podophyllotoxin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Time Factors; Treatment Outcome; Vincristine

We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs.. Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients.. The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M < 3 mg/dL and LDH normal), 61%; intermediate (beta 2M > or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M > or = 3 mg/dL and LDH above normal), 0%.. MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Mesna; Methylprednisolone; Middle Aged; Mitoxantrone; Prednisolone; Prospective Studies; Recurrence; Salvage Therapy; Vincristine

To purpose of this study was to develop a more effective approach to the treatment of patients with poor-prognosis aggressive non-Hodgkin's lymphoma (NHL).. Thirty newly diagnosed patients with bulky (> or = 10 cm) advanced-stage aggressive NHL were enrolled onto a pilot study. The study was designed to determine the maximum-tolerated dosages (MTD) of cyclophosphamide and doxorubicin that could be used in a high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with granulocyte colony-stimulating factor (G-CSF) support and to assess preliminarily the efficacy of the regimen.. In the initial dose-finding portion of the study, cumulative thrombocytopenia was the dose-limiting toxicity. At the MTD, the regimen included four 21-day cycles of cyclophosphamide 4 gm/m2, doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg for 5 days with mesna and G-CSF support. At the MTD, 65% of treatment cycles were complicated by febrile neutropenia, 84% of patients received at least one platelet transfusion for platelet counts less than 20,000/microL, and there was one treatment-related death. Nineteen of 22 (86%; 90% confidence interval [CI], 68 to 96) patients treated at the MTD achieved an initial complete response (CR), and 79% (90% CI, 58 to 92) of the complete responders and 69% of all patients remain progression-free with 20 months median follow-up.. The high-dose CHOP regimen may be an effective alternative for patients with poor-prognosis aggressive NHL.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hematopoietic Stem Cells; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin; Male; Mesna; Middle Aged; Pilot Projects; Prednisone; Prognosis; Vincristine

The effect of mesna on intracellular accumulation of cytosine arabinoside (Ara-C) in murine normal and neoplastic lymphocytes was studied. Simultaneous exposure of cells to mesna at concentrations ranging from 0.25 to 1.0 mM and 3H-Ara-C (40.0 nM) resulted in a strong inhibition of Ara-C uptake in normal lymphocytes. Under the same experimental conditions, mesna did not affect the Ara-C uptake in neoplastic cells (cultured L5178Y mouse leukaemia cells and neoplastically transformed thymus cells). It was found that the inhibitory effect of mesna was not cell cycle-dependent, since mesna reduced the Ara-C uptake in both normal quiescent and PHA-stimulated cells. We therefore concluded that mesna may selectively reduce Ara-C uptake by normal cells in vitro.

Topics: Animals; Cells, Cultured; Cytarabine; Dose-Response Relationship, Drug; Female; Leukemia L5178; Lymphocyte Activation; Lymphocytes; Lymphoma, Non-Hodgkin; Male; Mesna; Mice; Phytohemagglutinins; Tumor Cells, Cultured

The approach we have followed in developing treatment strategies for lymphoma consists of testing new combinations in patients with recurrent disease and, if these are found to be effective, advancing them to front-line therapy. Three series of salvage regimens tested at the M. D. Anderson Cancer Center (MDACC) will be described. These were initially based on ifosfamide/etoposide, later on high-dose cytarabine/cisplatin, and more recently on a novel strategy that first uses MINE (mesna/ifosfamide/Novantrone [mitoxantrone; Lederle International, Wayne, NJ]/etoposide) for induction of remission and, following the attainment of the maximum response to MINE, changes treatment to a non--cross-resistant combination known as ESHAP (etoposide/Solu-medrol ([methylprednisolone]/high-dose cytarabine/cisplatin). The front-line management of intermediate-grade lymphoma at MDACC currently is based on prognostic factors. The criteria for selecting categories of less favorable patients will be discussed. A new regimen, alternating triple therapy based on three non--cross-resistant drug regimens, currently is being explored for these patients. Already this regimen has shown an early advantage in the worst category of cases, those with M.D. Anderson stage D (high tumor burden, high levels of lactate dehydrogenase). The data, however, remain preliminary.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Clinical Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Mesna; Methylprednisolone; Middle Aged; Mitoxantrone; Prednisone; Salvage Therapy; Texas; Vincristine

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

We studied the efficacy of mesna as a protectant for urotoxicity in pediatric patients receiving chemotherapy including oxazaphosphorines. Nineteen patients with malignant diseases (5 neuroblastoma, 3 acute lymphocytic leukemia, 4 acute non-lymphocytic leukemia, 2 non-Hodgkin lymphoma, 3 osteosarcoma and 2 rhabdomyosarcoma) were treated with a total of 106 courses of therapy between June of 1986 and May of 1989. Of these, no gross hematuria were seen. Microhematuria transiently occurred only in 2 courses (5%) of 1 patient (2%). These data indicated that mesna was highly effective for urotoxicity of oxazaphosphorines without any side effects, especially in pediatric patients.

Topics: Bone Neoplasms; Child; Cyclophosphamide; Cystitis; Female; Hematuria; Humans; Ifosfamide; Leukemia; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Neuroblastoma; Osteosarcoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rhabdomyosarcoma

Ifosfamide (1.25 g/m2 intravenously/day x 5) with mesna (20% of the ifosfamide dose x six doses on each day of ifosfamide therapy) was administered to 46 previously treated patients with non-Hodgkin's lymphoma of which 31 were eligible and evaluable. A 29% response rate (9/31) was observed (2 CR and 7 PR) with a median duration of response of 2.5 months. Myelosuppression was dose-limiting. Hemorrhagic cystitis was observed in three patients (10%). Nausea and vomiting was generally mild or moderate. One patient developed transient neurotoxic symptoms with confusion and disorientation. An additional patient developed an anaphylactic-type reaction with shortness of breath and respiratory strider during the fourth course of therapy. Ifosfamide, as a single agent, produces remissions of limited duration in non-Hodgkin's lymphoma in patients in second or third relapse.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Drug Evaluation; Hematologic Diseases; Hematuria; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Mercaptoethanol; Mesna; Middle Aged

Topics: Adult; Aged; Carcinoma, Bronchogenic; Female; Hematuria; Humans; Ifosfamide; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Middle Aged; Neoplasms; Ovarian Neoplasms; Testicular Neoplasms