levoleucovorin and Lymphoma

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents; Cyclophosphamide; Drug Therapy, Combination; Hodgkin Disease; Humans; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma; Methotrexate; Middle Aged; Neoplasm Staging; Nitrogen Mustard Compounds; Prednisone; Procarbazine; Remission, Spontaneous; Vincristine

Patients with malignant lymphoma, diffuse type, have an unfavorable prognosis when compared to those patients with modular patterns. Prior to the introduction of combination chemotherapy, 50% survival rates for MC-D or PDL-D were about 2 years, HL-D about 1 year. Aggressive combination chemotherapy for advanced MC-D or PDL-D results in complete remission rates of 22-82%, with median survivals of 1-2 years. Patients with localized HL-D are probably curable with radiotherapy alone in 75% of cases. Patients with advanced disease are best treated with intensive combination chemotherapy, achieving a long-lasting complete remission in over one-half of cases, with median survivals now at 1-3 years. Many of these patients are probably cured, central nervous system relapse may now be a concern. The results of treatment of advanced histiocytic lymphoma are now approaching the results reported for advanced Hodgkin disease.

Topics: Antineoplastic Agents; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Neoplasms; Prednisone; Remission, Spontaneous; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

Topics: Antibodies, Neoplasm; B-Lymphocytes; Cyclophosphamide; DNA, Neoplasm; Doxorubicin; Drug Therapy, Combination; Humans; Immunotherapy; Leucovorin; Leukemia; Lymphoma; Methotrexate; T-Lymphocytes

The majority of the available data on primary central nervous system lymphoma (PCNSL) derive from small unicentric or oligocentric studies. In this multicentre study, we evaluated the response, survival and toxicity in PCNSL patients after carmustine, methotrexate 1.5 g/m2, procarbazine and dexamethasone (BMPD) chemotherapy and searched for prognostic factors. Fifty-six patients received the BMPD protocol (dexamethasone was given only in course 1). The overall complete response rate to chemotherapy was 61% (34/56). Ten complete responders received whole-brain irradiation and 24 were not irradiated. Responders to chemotherapy had significantly longer median overall survival than non-responders (18.2 vs. 9.9 months, P = 0.02). Median survival was significantly longer at institutions accruing at least four patients than at those with fewer patients (31.5 vs. 9.5 months, P = 0.03).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Central Nervous System Neoplasms; Combined Modality Therapy; Dexamethasone; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Procarbazine; Survival Rate; Treatment Outcome

To determine whether a lower dose of hyperfractionated whole brain radiation reduces central nervous system morbidity without compromising survival for primary CNS lymphoma (PCNSL) patients receiving combined modality treatment.. One hundred and two patients received a course of pre-radiation chemotherapy, followed by whole brain radiation, followed by cytosine-arabinoside. Initial radiation dose was 45 Gy/25 fractions (RT) then the study was amended to reduce this dose for complete responders to induction chemotherapy to 36 Gy/30 fractions/3 weeks (HFX). Eighty-two patients received radiotherapy and were evaluable for toxicity analysis (66 RT patients and 16 HFX patients). MMSE scores and survival for the 40 patients who received radiotherapy after complete response to chemotherapy (27 RT and 13 HFX) were compared. There were no notable differences in pre-treatment patient characteristics between the RT and HFX groups.. Neurotoxicity: By 4 years, there were 8/82 (10%) grade 5 neurotoxicities which included 2/16 (13%) grade 5 encephalopathies and 0/27 in the RT group of complete responders to chemotherapy. Survival: There was no statistically significant difference in overall or progression-free survival (PFS) between the chemotherapy-complete responders who received RT and HFX. Cognitive function testing: MMSE scores improved at 8 months across both treatment groups. Analysis of the area under the MMSE curve at 8 months showed no statistically significant difference between RT and HFX groups (P=0.81). Leukoencephalopathy occurred later in the HFX group than in the RT patients.. Although the HFX schedule represented a 25% reduction in biologically effective tumor dose in comparison, PFS and overall survival were not significantly affected. The HFX regimen delayed but did not eliminate severe neurotoxicity from chemoradiation in PCNSL patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain; Brain Neoplasms; Cognition; Combined Modality Therapy; Disease Progression; Dose Fractionation, Radiation; Humans; Leucovorin; Lymphoma; Methotrexate; Procarbazine; Radiation Injuries; Survival Rate; Vincristine

We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Nausea; Ondansetron; Prednisolone; Prednisone; Prognosis; Vincristine; Vomiting, Anticipatory

To compare a short intensified regimen followed by sequential consolidation therapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone [ACVBP]) to the standard regimen of methotrexate, bleomycin, cyclophosphamide, and etoposide (m-BACOD) in patients with low-risk aggressive lymphoma.. A total of 752 patients with intermediate- or high-grade lymphoma and no adverse prognostic factors (Eastern Cooperative Oncology Group performance status of 2 to 4, >/= two extranodal sites of disease, tumor burden >/= 10 cm in largest dimension, bone marrow or CNS involvement, Burkitt's or lymphoblastic subtypes) were registered. Of 673 eligible patients, 332 received ACVBP and 341 received m-BACOD.. The complete remission rate was identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate was 65% in the ACVBP group and 61% in the m-BACOD group (P =.16). The 5-year overall survival rate was 75% in the ACVBP group and 73% in the m-BACOD group (P =.47). ACVBP was responsible for more severe and life-threatening infections (P <.01), but m-BACOD caused more pulmonary toxicity (P <.001). The number of treatment-related deaths did not differ between the two regimens. A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index.. In this population of patients with low-risk aggressive lymphoma, toxicities of the regimens are different, but the rates of response and survival are identical. The survival advantage of ACVBP over standard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospective studies specifically designed for this purpose.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Humans; Immunophenotyping; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Multivariate Analysis; Prednisone; Prospective Studies; Remission Induction; Survival Analysis; Vincristine; Vindesine

To assess the efficacy and toxicity of combined modality therapy with short intensive primary chemotherapy in the treatment of primary CNS lymphoma (PCL).. Prospective study of 31 nonimmunodeficient patients with PCL treated with initial chemotherapy (13 shortened MACOP-B; and 18 modified MACOP with high dose methotrexate) followed by radiotherapy (whole brain and a boost). Patients were aged 18-72 years (median 51 years). Eight patients had positive CSF cytology of which one had spinal meningeal disease; one patient had vitreous involvement.. The overall complete response (CR) rate after chemotherapy and radiotherapy was 69% (95% Confidence Interval: 49-84%). At a median follow-up of 24 months (4 months to 10 years) median survival was 23 months and 5-year survival 34%. Age, sex, performance status, number of lesions, CSF cytology, and extent of surgery were not of prognostic significance for survival on univariate analysis. Eleven patients developed mucositis (Grade 3+) and 21 hematological toxicity (Grade 3+) with 22 septicemic episodes in 15 patients. Three patients developed dementia, one assumed to be treatment related, and two due to recurrent disease.. The survival results of short intensive primary chemotherapy followed by radiotherapy are similar to the results of chemotherapy in Stage IV aggressive systemic non-Hodgkin's lymphoma, although the treatment was associated with high morbidity. The apparently favorable results when compared to radiotherapy alone may at least in part be due to selection of patients with good prognostic factors. To confirm the benefit of combined chemotherapy and radiotherapy over either of the two modalities alone requires evaluation in large prospective and ideally randomized studies.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brain Neoplasms; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Vincristine

From December 1995 to July 1997, six patients with primary malignant lymphoma in the central nervous system were treated with 2 to 5 cycles of the M-CHOP regimen (methotrexate 3 g/m2 on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 40 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and predonisolone 60 mg on day 1 to 14: folic acid was given 3 hours after methotrexate at 10 mg/m2 every 3 hours for 9 doses intravenously). Five patients achieved complete remission (CR) and one experienced partial remission (PR). Posttherapeutic studies were performed in all patients with an average follow-up period of 20.1 months (range 8.1-26.8 months) after confirming the diagnosis. There was no evidence of recurrence of the tumors or growth of residual tumors in any of the patients in this period. The major toxic effect was myelosupression with leukopenia. Alopecia was observed in all patients. No treatment-related deaths were observed. The M-CHOP regimen seems to be a promising treatment for primary malignant lymphoma in the central nervous system.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Vincristine

Prior studies have suggested that pre-irradiation methotrexate (MTX)-based chemotherapy improves duration of response and survival in primary central nervous system lymphoma (PCNSL). To circumvent the potential emergence of drug resistance, we combined high-dose MTX with agents highly active against systemic lymphoma. Patients received three week cycles of CHOD (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [2 mg maximum] on day 1; dexamethasone 10 mg/m2 days 1-5), and MTX (3.5 gm/m2) with leucovorin rescue on day 8 (or on recovery from the CHOD nadir). Whole brain irradiation (WBRT) was planned after at least three cycles. Eighteen patients were treated. Complete responses were seen in eleven patients, and partial responses in three. Four progressed during therapy, three succumbing to progressive disease and one subsequently responding to WBRT. Response duration was 37.5 months in those responding to therapy. The time to progression for all eighteen patients was 19.5 months. Medial survival was 25.5 months. Disease-free survival was 50% at 38 months in MCHOD responders. Grade 3 or 4 myelotoxicity was seen in 19 of 50 cycles. There were three instances of neutropenic fever, three of azotemia, two of deep vein thrombosis, and one each of community-acquired pneumonia, intracranial hemorrhage, superior vena cava syndrome, and hepatotoxicity. Late radiation-related toxicities were seen in two patients. Pre-irradiation MCHOD has activity against PCNSL, but appears to be no better than MTX monotherapy and has greater toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Recurrence; Survival Analysis; Vincristine

--To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS).. --A phase II prospective clinical trial, with median follow-up of 33 months.. --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases.. --Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response.. --A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m2 intravenously (IV); doxorubicin, 25 mg/m2 IV; vincristine sulfate, 1.4 mg/m2 IV; bleomycin, 4 mg/m2 IV; dexamethasone, 3 mg/m2 orally on days 1 through 5; methotrexate, 500 mg/m2 IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy.. --Response rate and number of opportunistic infections.. --Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival.. --Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Diseases; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; HIV Seropositivity; Humans; Leucovorin; Lymphoma; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Opportunistic Infections; Prospective Studies; Vincristine; Zidovudine

We report the results of treatment with MACOP-B in 11 young patients with low grade lymphoma (LGL). Complete remission was obtained in 4 (57%) and partial remission in 3 (42.8%) of 7 evaluable patients. However, this aggressive chemotherapy has not offered any advantage because of an unacceptably high treatment-related morbidity and mortality (17%). Serious infection during neutropenia was the most common complication.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Granulocytes; Humans; Infections; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Remission Induction; Survival Analysis; Vincristine

Seventy-one patients with advanced stage diffuse large cell lymphoma were treated with MACOP-B. Sixty-nine per cent of patients achieved a complete response (CR), 10% a partial remission, while 11% had no response and 10% died because of toxicity. The CR rate was adversely affected by immunoblastic type, poor performance status and bone marrow involvement. Two-year survival for all 71 patients was 55% and 2-year disease-free survival (DFS) for the 49 CRs was 73%. Relapses were lower (P less than 0.05) in patients achieving CR in 8 weeks or less (DFS 83% vs. 59%) and in patients without tumor bulk (DFS 87% vs. 54%). Overall toxicity was acceptable with mucositis proving to be the most frequent severe side-effect. However, treatment-related deaths were unacceptably high in patients over 59 years of age (30% vs. 7%). Thus for the elderly MACOP-B is potentially lethal and must be used cautiously. These preliminary results confirm the effectiveness of MACOP-B. The delay of response and/or the presence of tumor bulk may be important prognostic factors in identifying a subset of poor risk patients with a high incidence of relapse.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Evaluation; Female; Humans; Italy; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Multicenter Studies as Topic; Prednisone; Vincristine

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Pilot Projects

Topics: Adult; Aged; Clinical Trials as Topic; Female; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Myeloid, Acute; Lymphoma; Male; Methotrexate; Middle Aged

The cooperative study group, consisting of 11 institutes, conducted a study by the high-dose methotrexate (MTX) with citrovorum factor (CF) rescue therapy on acute leukemia and malignant lymphoma that were resistant to other anti-cancer chemotherapy. In acute leukemia the rates of complete remission (CR) and partial remission (PR) were 16.7% and 26.7%, respectively, and in malignant lymphoma the response rate (excellent plus good response) was 38.9%. This therapy would be safely carried out by alkalinization of urine and adequate hydration under sufficient clinical surveillance. From the results of the present study, high-dose MTX-CF therapy seems to be one of effective regimens for acute leukemia and malignant lymphoma that are resistant to the conventional doses of MTX or other anti--cancer agents. Also, with this therapy, treatment or prophylaxis of symptoms of central nervous system and of other pharmacological sanctuaries can be expected, which may be one of the useful points of H-MTX-CF therapy.

Topics: Acute Disease; Adolescent; Adult; Child; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukemia; Lymphoma; Male; Methotrexate

Total parenteral nutrition (TPN) has been suggested as a useful addition to chemotherapy of malignant disease in the hope of decreasing drug toxicity and increasing drug tolerance. In this study, 17 of 36 patients given chemotherapy for advanced diffuse lymphoma were randomly selected to receive TPN. The dose of the chemotherapeutic agents to be administered was decreased according to predetermined toxicity guidelines. A comparison of drug dosage in the group receiving TPN and the group receiving standard nutrition is a measure of drug tolerance in these patients. Drug dosage was evaluable in 15 TPN and 18 standard nutrition patients. No difference in tolerance of any specific drug or total drug dose occurred when all patients in both groups were compared. Similar comparisons in subgroups of malnourished patients and responding patients also revealed no difference. A cycle-by-cycle analysis demonstrated no difference in any phase of therapy. The wbc count, platelet count, and albumin level, on the first day of each cycle, the nadir during cycles and the day of nadir were compared in TPN and standard nutrition patients. No differences were found. This study does not suggest improved drug tolerance in lymphoma patients as a result of TPN support. Further controlled studies are needed to determine which groups of cancer patients might benefit from TPN and how these benefits occur.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Drug Tolerance; Etoposide; Humans; Leucovorin; Leukocyte Count; Lymphoma; Mechlorethamine; Methotrexate; Nutrition Disorders; Parenteral Nutrition; Platelet Count; Prednisone; Procarbazine; Prospective Studies; Random Allocation; Serum Albumin; Vincristine

Topics: Adult; Aged; Antineoplastic Agents; Bone Marrow; Burkitt Lymphoma; Child; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prognosis; Remission, Spontaneous; Time Factors

In patients exposed to high-dose methotrexate (HDMTX; >1g/m. This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 μmol/L) and incident AKI after each HDMTX dose.. The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001).. Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Topics: Acute Kidney Injury; Aged; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Retrospective Studies

The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was established. Cell viability after MTX treatment with LV rescue was evaluated using sodium butyrate (NaBu), a histone-deacetylase inhibitor that induces polyglutamylation by elevating FPGS expression. The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p < 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p < 0.01). In vitro, the relief effect of LV after MTX administration was significantly enhanced after FPGS knockdown in al cell lines, whereas enhancement of FPGS expression by NaBu treatment significantly reduced this relief effect. These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combination therapy with HD-MTX and polyglutamylation-inducing agents might represent a promising strategy for PCNSL treatment.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cell Line, Tumor; Cell Survival; Central Nervous System Neoplasms; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Treatment Outcome; Vitamin B Complex

Topics: Brain Neoplasms; Combined Modality Therapy; Humans; Leucovorin; Lymphoma; Methotrexate; Treatment Outcome

We assessed the outcome of high-dose methotrexate (HD-MTX) chemotherapy with or without radiotherapy (RT) in primary central nervous system lymphoma (PCNSL) patients.. Fifty-one HIV-negative patients with an average age of 50.3 years were treated with chemotherapy regimen included 2500 mg/m(2) MTX with Leucovorin rescue and 1.4 mg/m(2) vincristine (day two), which was administered every other week for 6 weeks. Only the patients who were younger than 60 years received RT. All patients received two cycles of 3000 mg/m(2) cytarabine at the end of the treatment for two successive days.. Diffuse large B-cell lymphoma was the most common histologic subtype (90.2%), and twenty-six (51.0%)patients had multiple brain lesions. The median survival of patients who were younger than 60 years was 37 months. For patients who were older than 60 years, the median survival was 20 months. The median survival of men and women were 30 and 34 months, respectively. There was no significant difference in survival of patients in terms of age and sex. Overall, sixteen patients (31%) out of fifty-one patients died, five of them were older than 60 years and eleven were younger than 60 years. Twenty-five (49%) of all patients experienced relapse, and 10 (40%) of them died after rechemotherapy.. The base of our chemotherapy regimen was HD-MTX as the regular doses of MTX cannot penetrate the blood brain barrier (BBB). Our results indicated that the combination of HD-MTX with RT may not influence the outcome of PCNSL; thus, RT cannot be the first line therapy.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Central Nervous System Neoplasms; Cytarabine; Dose-Response Relationship, Drug; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Radiotherapy, Adjuvant; Retrospective Studies; Vincristine

Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found.. One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy.. The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS.. A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Chemotherapy, Adjuvant; Cognition; Cranial Irradiation; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Female; Humans; Kaplan-Meier Estimate; Karnofsky Performance Status; Leucovorin; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Radiotherapy, Adjuvant; Retrospective Studies; Salvage Therapy; Treatment Outcome; Vincristine

Intoxication due to insufficient renal clearance developed in 2 patients, a 54-year-old man and a 61-year-old woman, who were under treatment with methotrexate (MTX) for a primary cerebral lymphoma and a recurrence of large-cell B-cell-non-Hodgkin lymphoma, respectively. Both were treated with folinic acid rescue, thymidine, and alkalisation of the urine. MTX is a cytotoxic drug that is often used in oncology and rheumatology. Significant and even lethal toxicity can develop when the elimination ofMTX is delayed or when supportive care, such as folinic acid rescue, is inadequate. Delayed elimination can be caused by reduced renal function, by the 'third space' phenomenon such as in case of ascites, pleural fluid accumulation and oedema, and by drug-drug interactions leading to reduced renal function or a disturbance in the plasma protein binding ofMTX. Once toxicity has developed, the therapy must be directed at protection of the normal tissues, restoration of renal function and hence the renal elimination ofMTX, restoration of the alkalisation of the urine, and general supportive therapy.

Topics: Antimetabolites, Antineoplastic; Brain Neoplasms; Female; Humans; Kidney; Leucovorin; Lymphoma; Lymphoma, B-Cell; Male; Methotrexate; Middle Aged; Renal Insufficiency; Thymidine; Vitamin B Complex

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Retrospective Studies; Time Factors; Vincristine

A 54-year-old patient with primary cerebral lymphoma was treated with two 4-weekly cycles of high-dose intravenous cytarabine (12 g/m2) and methotrexate (3 g/m2). The administration of the first course proceeded without notable complications. Before the administration of methotrexate in the second cycle blood cell counts and chemistry showed no abnormalities except for slightly increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels which was attributed to diphantoin comedication. The patient developed symptoms of acute renal failure 7 h after methotrexate infusion which resulted in a very high serum methotrexate level (39.84 micromol/l) at 20 h after infusion. Rescue therapy was intensified: the leucovorin dosage was increased (1,200 mg continuous i.v. infusion every 24 h) and combined with thymidine rescue therapy (8 g/m2 per day continuous i.v. infusion every 24 h). Urine alkalinization was increased and diphantoin therapy was stopped. Leucovorin eye drops and mouth washes were started 5 days after methotrexate administration to prevent conjunctivitis and mucositis as a result of high methotrexate levels (>2.4 micromol/l). In spite of the fact that serum methotrexate levels remained persistently higher than 0.1 micromol/l for 12 days, the patient experienced no further short-term systemic toxicity except for anaemia (grade 3 according to NCI Common Toxicity Criteria). After day 12 intensified rescue therapy and the frequency of alkalinization were decreased to standard procedures and stopped on day 19. It is concluded that i.v. administration with high-dose methotrexate can result in unpredictable acute toxicity. In our patient, acute methotrexate toxicity was treated successfully by intensification of classical leucovorin rescue therapy in combination with thymidine infusion. In addition, leucovorin mouth washes and eye drops may have prevented mucositis and conjunctivitis, respectively.

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Brain Neoplasms; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma; Methotrexate; Middle Aged; Thymidine

Patients treated for Hodgkin's disease and non-Hodgkin lymphomas were followed for 5 years after start of therapy. The patients received combinations of anticancer drugs for curative intent for 6 months (Hodgkin's disease) or 7 months (non-Hodgkin lymphomas).. Cumulated data of 22 surviving patients (mean age, 49 years) were compared with that of 17 patients (mean age, 52 years) who had died or were terminally ill at the 5-year examination. Saliva samples were taken at baseline, and 4, 6, 12, and 60 months after start of chemotherapy. Salivary flow rate and a variety of biochemical constituents were analyzed.. The results showed no long-term effect of anticancer treatment on salivary flow rates. Neither was there any difference between the surviving or deceased patients' baseline values (1.5 +/- 0.7 mL/minute versus 1.5 +/- 0.8 mL/minute) and after chemotherapy. Lysozyme, IgA, IgG, and IgM concentrations decreased after chemotherapy. Significantly lower values were observed at the 5-year examination than at baseline. This was particularly evident in IgA, which is the major immunoglobulin in saliva; mean IgA was 70.5 +/- 52.8 mg/mL at baseline, 35.8 +/- 15.0 mg/mL 5 years later (p < 0.001). Salivary total protein and amylase concentrations were significantly decreased (p < 0.001 and p < 0.05, respectively), whereas albumin concentration was significantly increased at the 5-year examination (p < 0.05). When the salivary biochemical results were compared between the surviving and deceased patients, no statistically significant differences were observed. At baseline, however, the mean immunoglobulin values were lower in patients who later died, in comparison with those who survived.. These results showed that modern anticancer therapy need not cause severe side effects on salivary flow rates and composition. In addition, apart from the long-term immunosuppression, no significant decreases were expressed in salivary defensive factors.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Amylases; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Dexamethasone; Doxorubicin; Epirubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Immunoglobulin A, Secretory; Leucovorin; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Middle Aged; Muramidase; Prednisone; Procarbazine; Saliva; Salivary Proteins and Peptides; Secretory Rate; Statistics, Nonparametric; Vinblastine; Vincristine

Thromboembolic complications and decrease in protein C and S have been observed in patients while receiving combination chemotherapy for breast cancer. We investigated whether initial cytotoxic treatment of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is also associated with changes in these anticoagulant parameters. For this purpose 25 patients with intermediate to high grade NHL and seven with HD, undergoing primary treatment with cytotoxic drugs were evaluated at three time-points: pre-therapy, mid-therapy and post-therapy. In contrast to the breast cancer patients, no significant changes in protein C, protein S and antithrombin III levels were observed in the NHL patients during the various stages of therapy. However in HD patients, the mean protein C values had a tendency to be higher at mid-therapy compared to pre-therapy and protein S levels had a tendency to be higher at mid-therapy compared to post-therapy. In lymphoma patients receiving primary cytotoxic treatment we did not find changes in anticoagulant parameters that can explain a chemotherapy-induced hypercoagulable state, as has been reported in breast cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha-2-Antiplasmin; Antineoplastic Combined Chemotherapy Protocols; Antithrombin III; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Fibrin Fibrinogen Degradation Products; Hodgkin Disease; Humans; Leucovorin; Lymphoma; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Middle Aged; Mitoxantrone; Partial Thromboplastin Time; Plasminogen; Prednisone; Procarbazine; Protein C; Protein S; Thrombophilia; Time Factors; Vinblastine; Vincristine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Leucovorin; Lymphoma; Methotrexate; Middle Aged; Vincristine

The frequency of numerical and structural chromosomal abnormalities was studied in the sperm of a lymphoma patient 3 years after MACOP-B chemotherapy (CT). Sperm karyotyping was performed by fusion of human sperm with hamster oocytes and analysis of 193 Q-banded sperm chromosomes. Multicolor fluorescence in situ hybridization (FISH) was performed on 10,228 sperm for analysis of disomy frequencies for chromosomes 1 and 12 and on 10,664 sperm for chromosomes X and Y. Sperm karyotyping demonstrated numerical abnormalities in 7.3% of the spreads, 6.7% hypohaploid and 0.5% hyperhaploid, giving a conservative estimate of aneuploidy of 1%. Structural chromosomal abnormalities were present in 7.3% of the karyotypes and 0.5% had both numerical and structural abnormalities. Results of FISH analyses yielded disomy frequencies of 0.10%, 0.11%, 0.04%, 0.05%, and 0.18% for chromosomes 1, 12, X, Y, and XY, respectively. The frequency of diploid sperm was 0.09%. The frequency of abnormalities was not significantly increased compared to control donors for any of the studies. Also, the frequencies of X- and Y-bearing sperm did not differ significantly from 50% in the sperm karyotyping or FISH studies.

Topics: Aneuploidy; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chromosome Aberrations; Cyclophosphamide; Doxorubicin; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leucovorin; Lymphoma; Male; Methotrexate; Prednisone; Spermatozoa; Vincristine

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Myelodysplastic Syndromes; Prednisone; Procarbazine; Rectal Neoplasms; Risk Factors; Seminoma; Testicular Neoplasms; Transplantation, Autologous; Vincristine

The treatment of primary central nervous system lymphoma with chemotherapy prior to whole-brain radiation therapy (WBRT) has improved outcome considerably in this previously fatal disease. Complete or partial responses to intravenous methotrexate (3.5 gm/sq m with leucovorin rescue every 3 weeks for two to four cycles) were seen in 12 of 13 patients originally treated. A total of 25 patients (including the original 13) have now been treated with one to six cycles of methotrexate every 10 to 21 days prior to WBRT. Twenty-two had partial or complete responses, with a median duration of response of 32 months. Median survival time was 33 months (42.5 months in those responding to therapy). Nine patients are alive and without evidence of disease 9 to 122 months following therapy. Acute and long-term toxicities were minimal. Systemic methotrexate administration prior to WBRT is well tolerated and produces long-term survival.

Topics: Adult; Aged; Aged, 80 and over; Central Nervous System Neoplasms; Combined Modality Therapy; Cranial Irradiation; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy Dosage; Remission Induction; Survival Rate; Treatment Outcome

In a random HIV-seropositive population, malignant lymphomas were diagnosed in 31 patients, of whom 24 (77%) had non-Hodgkin lymphoma (NHL) and 7 (23%) Hodgkin lymphoma (HL). The prevalence of NHL among AIDS patients was 8% (23/279 cases), with a prevalence of 17% among autopsied patients (16/96 cases). No patient with HL had AIDS at the time of diagnosis. In 7 of 23 AIDS patients with NHL (30%) the diagnosis was made only post mortem; among these were all 5 patients with primary CNS NHL. Median survival from the time of diagnosis was 1 month for patients with NHL and 3 months for those with HL. In individual patients, survival for several years may be possible with chemotherapy. Certain patients with NHL appear to benefit from intensive chemotherapy with a combination of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOPB protocol). Appropriate, therapeutic strategies taking into account the patients' individual conditions, including the overall prognosis, urgently requires development. Metastatic CNS involvement, which was the primary cause of death in 5 of 11 patients with NHL (45%) receiving chemotherapy, represents a serious limitation to successful treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Female; HIV Seropositivity; Hodgkin Disease; Humans; Leucovorin; Lymphoma; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Prognosis; Vincristine

Combination chemotherapy with or without radiotherapy has had only modest efficacy in the treatment of primary CNS lymphoma. Median survival of these patients, treated primarily with radiotherapy, is 13 months; 5-year survival is less than 5%. Thirty consecutive non-acquired immune deficiency syndrome patients with primary CNS lymphoma were treated with barrier-dependent chemotherapy using intraarterial mannitol to open the blood-brain barrier (BBB). Follow-up included extensive neuropsychologic testing of all patients. Thirteen patients received cranial radiation 1 to 9 months before referral (group 1). Seventeen patients received initial BBB disruption chemotherapy with subsequent radiation only for tumor progression or recurrence (group 2). The difference in median survivals from diagnosis--17.8 months for group 1 and 44.5 months for group 2--was statistically significant (P = .039). Group 1 survival is comparable with the 20-month median survival of a historical series of patients (n = 208) treated with radiotherapy with or without chemotherapy. Group 2 patient survival represents an advance in the survival of CNS lymphoma and was associated with preservation of cognitive function in six of seven nonirradiated complete responders observed for 1 to 7 years. Patient toxicity was manageable in this intensive therapeutic regimen. In this series, a plateau in survival curves suggests that a major portion of these patients may be cured without the neuropsychologic sequelae associated with cranial radiation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain Neoplasms; Cognition; Cyclophosphamide; Dexamethasone; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neuropsychological Tests; Procarbazine; Prognosis; Proportional Hazards Models; Survival Rate

We present a patient with large-cell lymphoma in remission who, over several weeks, developed widespread multifocal polyneuropathy. There was involvement of all four limbs, most severely the left upper extremity that had become useless. Biopsy of the left saphenous nerve within an area of sensory loss showed lymphoma in the endoneurium. There was no other evidence of recurrent lymphoma despite extensive investigation, including bone marrow, lumbar puncture, magnetic resonance imaging of the spine, and computed tomography of the abdomen and pelvis. Intensive systemic chemotherapy was accompanied by nearly complete recovery. Biopsy of a symptomatic nerve is preferable to routine sural nerve biopsy in this condition because of its patchy distribution. Treatment with systematic chemotherapy can be effective.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cyclophosphamide; Cytarabine; Electrophysiology; Female; Humans; Leg; Leucovorin; Lymphoma; Methotrexate; Nervous System; Nervous System Neoplasms; Vincristine

Between 1986 and 1988 10 patients with primary cerebral lymphoma (PCL) were treated with initial MACOP-B chemotherapy followed by radiotherapy. All demonstrated radiological response to chemotherapy but this did not predict final clinical outcome. The overall median survival was 14 months. Patients with poor MRC neurological performance status (NPS) 2-4 had a median survival of 5 months. Three of 7 patients with NPS 0-1 died and the median survival is 18 months with a median follow-up of 13 months (10-35 months). The results were compared to 25 patients with primary cerebral lymphoma treated between 1963 and 1986 with radiotherapy as the main treatment modality. The overall median survival was 16 months. Patients presenting with poor NPS (2 and 3) had worse survival (median survival 8 months) compared to patients with good NPS (median survival 22 months; p less than 0.025). Patients diagnosed and treated from 1982 to 1986 also had significantly worse prognosis when compared to earlier treated patients. The preliminary results of combined modality therapy are so far not significantly different when compared to historical series and we have to await long-term outcome before recommending combined modality therapy as the treatment of choice.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Brain Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Vincristine

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; L-Lactate Dehydrogenase; Leucovorin; Leukocyte Count; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Neoplasm Staging; Survival Analysis; Vincristine

We have recently shown that methotrexate (MTX) inhibits interleukin-1 (IL-1) activity in vitro. This effect may play an important role in the rapid antiinflammatory action of MTX in rheumatoid arthritis. In the present study, we showed that the inhibition of IL-1 activity in vitro by MTX is dependent on folate pathways since, after the addition of leucovorin, the inhibitory effect of MTX was abolished. These findings may shed more light on the mechanism of action of MTX in rheumatoid arthritis. They also point to the fact that some IL-1 activities may be dependent on intracellular folate pathways.

Topics: Animals; Drug Interactions; Folic Acid; Interleukin-1; Interleukin-2; Leucovorin; Lymphoma; Methotrexate; Mice; Tumor Cells, Cultured

Topics: Humans; Leucovorin; Lymphoma; Methotrexate; Stomach Neoplasms

Twelve patients with primary small intestinal lymphoma were followed prospectively for 3 years. Endoscopic abnormalities were diagnostic of lymphoma in all cases where the duodenum was involved (83%). In three cases (25%) the disease extended to the stomach. One patient (8%) had diffuse small cell cleaved and 11 (92%) diffuse large cell lymphoma stages I (8%), II (25%), III (58%) and IV (8%). Nine of them were unresectable and primarily treated with combination chemotherapy; 67% achieved complete remission, 22% partial response and 11% no response. Only one patient relapsed and achieved a second remission. All complete remission patients are currently alive and free of disease at a median follow-up of 36 months. Overall survival for all patients is 58%, and disease-free survival is 50%. No instance of chemotherapy-related bleeding or perforation was seen. Tetracycline was necessary for the treatment of IPSID-associated diarrhea and malabsorption in spite of cytotoxic chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; Humans; Intestinal Neoplasms; Intestine, Small; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Saudi Arabia; Vincristine

A 22-year-old nulligravida presented with a stage IE/IIIB primary malignant lymphoma of the cervix which measured 8 cm in diameter. In order to preserve reproductive potential, a 12-week course of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin was administered. One month later a 4-cm-diameter left parametrial mass was excised at laparotomy; no tumor was detected in the specimens obtained. Menses resumed after an additional 6 months. The patient was clinically disease-free at the 33-month follow-up.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Methotrexate; Prednisone; Uterine Cervical Neoplasms; Vincristine

Localized lymphomas of diffuse and aggressive histology sometimes undergo early hematogenous dissemination such that local therapies (surgery alone or followed by radiation therapy) are not curative in 100% of cases. We have treated 47 clinical stage I or IE patients with aggressive lymphoma histologies (diffuse large-cell, diffuse mixed, diffuse immunoblastic, follicular large-cell, diffuse small-non-cleaved cell) with four monthly cycles of an eight-drug combination chemotherapy program consisting of cyclophosphamide, etoposide, doxorubicin, nitrogen mustard (mechlorethamine), procarbazine, high-dose methotrexate with leucovorin rescue, and prednisone (Pro-MACE-MOPP) administered systemically followed by 40 Gy involved-field radiation therapy. Forty-five (96%) patients achieved a complete remission and no patient has relapsed with a median follow-up time of 42 months (range, 8 to 90). Both patients failing to achieve a complete remission died of lymphoma, and one patient died free of lymphoma 45 months after diagnosis during coronary artery bypass surgery unrelated to lymphoma or its treatment. Hospital admissions were necessary to manage complications on nine of 188 (5%) cycles of treatment. There were no treatment-related deaths. ProMACE-MOPP plus involved-field radiation therapy is safe and effective treatment for localized aggressive lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Humans; Leucovorin; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Remission Induction; Vincristine

A case of pulmonary T-cell lymphoma in an Acquired Immune Deficiency Syndrome (AIDS) patient is presented. Morphologically, it belonged to the large cell, immunoblastic category of the Working Formulation and demonstrated a helper/inducer phenotype. Clinically there was no association with manifestations of human T-lymphotropic virus (HTLV)-I related lymphoma and the patient was seronegative for HTLV-I and HTLV-II antibodies. High-grade B-cell lymphomas occur with an increased frequency in patients with AIDS but the occurrence of a peripheral T-cell lymphoma in AIDS has not been documented before. The case is discussed in the context of current concepts of AIDS-related lymphomagenesis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; HIV; Humans; Immunohistochemistry; Leucovorin; Lung Neoplasms; Lymphoma; Male; Methotrexate; T-Lymphocytes; Vincristine

Acute methotrexate intoxication occurred in 4 patients despite adequate alkaline hyperhydration and classical folinic acid rescue. Three of these patients had no previous risk factor. Charcoal haemoperfusion with haemodialysis was promptly instituted and the methotrexate blood levels rapidly decreased, avoiding further renal damage and multisystemic involvement. Chemotherapy could subsequently be performed in 3 of the 4 patients without delay and toxicity. Charcoal haemofiltration appears to be an excellent treatment of methotrexate intoxication.

Topics: Aged; Charcoal; Child; Female; Hemoperfusion; Humans; Kidney Function Tests; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Renal Dialysis

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Combined Modality Therapy; Drug Interactions; Female; Humans; Iopamidol; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Osteosarcoma

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasms; Osteosarcoma

Twenty-two consecutive patients with high-grade, B-cell lymphomas related to the acquired immunodeficiency syndrome (AIDS) were accrued onto two sequential phase II studies, consisting of a standard regimen (M-BACOD, group no. 1, N = 13), or a novel, intensive regimen (group no. 2, N = 9), which included high-dose cytosine arabinoside (HD-Ara-C), and high-dose methotrexate (HD-MTX), in an attempt to prevent CNS relapse and improve response rates. Stage IV disease was present in 82%. Complete remission (CR) was achieved in seven of 13 patients (54%) in group no. 1, and in three of nine (33%) group no. 2 (P = NS). By multivariate analysis, the most significant factor in predicting response was a Karnofsky performance score (KPS) greater than 60 (P = .04). Three of the ten patients who achieved CR on either regimen have relapsed; in all, five of 13 patients (31%) in group no. 1 have achieved disease-free survival for more than 1 year, compared with one of nine (11%) in group no. 2. CNS progression occurred in six patients in group no. 2, and in two patients in group no. 1. Hematologic toxicity was significantly greater in group no. 2, and these patients had an increased risk of opportunistic infection (one in group no. 1 v seven in group no. 2; P less than .01). Survival was similar, with a median of 11 months in group no. 1 and 6 months in group no. 2. We conclude that the intensive regimen of combination chemotherapy described here is associated with significant risk of early death due to opportunistic infection in patients with AIDS-related lymphoma, and that progression in the CNS remains a major problem. Trials of combination chemotherapy of a less intensive nature, perhaps in combination with immunomodulators or antiretroviral agents should be explored.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; B-Lymphocytes; Bleomycin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Vincristine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Nail Diseases; Skin Diseases, Vesiculobullous

During the use of a therapeutic regimen of high-dose methotrexate (HD-MTX) with leucovorin rescue in two cases of osteogenic sarcoma and malignant lymphoma without central nervous system (CNS) involvement, serial EEG monitoring before and after MTX infusion was performed with special reference to occipital basic activity. The EEGs were analyzed as to the power average spectrum using an ATAC-450 (NIHON KOHDEN). At 48 hours after the initiation of MTX, there was a transient but statistically significant slowing, such as a drop in the dominant frequency and a decrease in the alpha/theta ratio. Complete recovery of EEG changes occurred within one week. No clinical symptoms suggestive of CNS impairment were noted in either case. These data suggest that EEG alterations might be a reflection of subclinical CNS impairment. Therefore, serial EEGs might be a good early indicator for the detection of leukoencephalopathy in high-risk patients.

Topics: Bone Neoplasms; Child; Child, Preschool; Electroencephalography; Female; Humans; Infusions, Intravenous; Leucovorin; Lymphoma; Male; Methotrexate; Osteosarcoma

One hundred twenty-one patients with diffuse large-cell lymphoma treated with m- or M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) were evaluated for pretreatment characteristics predictive for response and survival. Two characteristics, poor performance status and massive bulky disease, were negatively associated with response rate in a multivariate analysis. These two characteristics were also negatively associated with survival in multivariate analysis, as was another factor, an increased number of extranodal sites of disease. These three pretreatment characteristics were used to construct a model containing 12 categories of patients at increasing risk for relapse and shortened survival. These categories divided naturally into three broad groups of patients with respective 5-year survival rates of 68%, 55%, and 24%.

Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prognosis; Regression Analysis; T-Lymphocytes; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Drug Evaluation; Etoposide; Hodgkin Disease; Humans; Leucovorin; Lomustine; Lung Diseases; Lymphoma; Middle Aged

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Leucovorin; Lymphoma; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Vinblastine; Vincristine

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.

Topics: Actuarial Analysis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Staging; Neutropenia; Peripheral Nervous System Diseases; Prednisone; Prognosis; Thrombocytopenia; Vincristine

Ten patients with non-Hodgkin's lymphoma primarily affecting the orbital region were evaluated at Michael Reese Hospital and Medical Center, Chicago, between 1976 and 1983. Diagnoses were based on the histopathologic classification systems of the Working Formulation of the Non-Hodgkin's Lymphomas and Rappoport. Sequential staging procedures performed at the time of diagnosis included liver-spleen scans, Technecium-99 bone scans, gallium 67 scans, computerized axial tomograms of the orbit and abdomen, bone marrow examination and cerebral spinal fluid analyses. Adverse prognostic factors included the following: orbital bone erosions, Stage IV disease, and large cell or mixed cell, diffuse histologic features. The type of histopathologic findings combined with the results of sequential staging procedures is useful in identifying those patients who would benefit most from systemic chemotherapy.

Topics: Actuarial Analysis; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Staging; Orbital Neoplasms; Prednisone; Prognosis; Radionuclide Imaging; Vincristine

Normal marrow cell kinetics were studied by flow cytometry with computer analysis in 11 children with malignancies who received high-dose MTX followed by CF rescue. Nine children with hematological tumors in remission each received an infusion of MTX over 24 h, followed by delayed CF rescue. In 8 of the 9, an accumulation of cells in early to mid-S phase and a decrease of cells in G2/M phase were observed at 24-48 h after the beginning of the MTX infusion. At 144 h after MTX infusion this kinetic perturbation disappeared and the DNA histogram returned to the same state as before therapy. Two children who had malignant bone tumors without marrow infiltration each received an infusion of MTX over 6 h with early CF rescue following an initial IV injection of vincristine. They did not have any prominent perturbation of marrow cell kinetics after MTX exposure, except for a transient increase of cells in G2/M phase. These results confirm that with the high-dose MTX therapy described above for hematological malignancies the impairment of marrow cell kinetics was much more severe and was soon followed by complete recovery, whereas with the therapy for solid tumors the impairment was much slighter.

Topics: Adolescent; Age Factors; Bone Marrow; Cell Cycle; Child; Child, Preschool; DNA; Female; Flow Cytometry; Humans; Infant; Leucovorin; Leukemia; Leukocyte Count; Lymphoma; Male; Methotrexate; Mitotic Index; Platelet Count

Twenty-one patients with intermediate- and high-grade lymphomas were treated with modified cyclophosphamide, vincristine, methotrexate, leucovorin, and cytarabine (COMLA). This regimen utilizes the drugs used in COMLA in similar doses, but cyclophosphamide is given twice as frequently, cytarabine is given by continuous infusion, and the total duration of therapy is reduced to 16 weeks. Complete remission rates were 80% in patients with intermediate-grade lymphomas and 67% in patients with high-grade lymphomas. Persistent complete remission rates were 60% and 33%, respectively, with a median follow-up of 26 months for surviving patients. This regimen was myelotoxic, but there were no toxic deaths. Modified COMLA is a relatively nontoxic regimen producing excellent results in intermediate-grade lymphomas.

Topics: Actuarial Analysis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisone; Vincristine

Thirty-three patients with diffuse non-Hodgkin's lymphoma (stages I and II) received intermediate doses of oral methotrexate followed by leucovorin calcium every four weeks, on days 1 and 8, followed on day 15 by intravenous cyclophosphamide and vincristine sulfate. Prednisone was given for four weeks on alternate courses of treatment. A total of six such four-week courses was planned. Involved-field radiation (3000 or 3600 rad [30 or 36 Gy]) was given between three courses of chemotherapy to 18 patients who presented with tumors exceeding 7 cm in greatest diameter and who had responded to the initial chemotherapy. On completion of treatment, 27 patients (82%) were in complete remission; all the failures were in patients with large intra-abdominal masses. The presence of high lactate dehydrogenase levels, large tumor size, and age over 60 years had a suggestive negative correlation with the achievement of complete remission. The median follow-up was 26 months (range, ten to 59 months). At 48 months, the actuarial disease-free survival, remission duration, and overall survival were 53%, 72%, and 68% respectively. No deaths from toxic effects and no septic episodes were observed during treatment. The complete remission rate achieved with this program is comparable with those of other intensive programs of treatment reported previously.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Prospective Studies; Time Factors; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Humans; Leucovorin; Lymphoma; Methotrexate; Prednisone; Time Factors; Vincristine

Until the mid 1960s the advanced stage, high grade non-Hodgkin's lymphomas were rapidly progressive, fatal diseases with few patients remaining alive at 5 years. Studies conducted at the NCI demonstrated that 47% of all patients with advanced stages of diffuse mixed, large cell, and undifferentiated non-Burkitt's lymphoma could achieve a complete remission documented by reevaluation of all initially involved sites following treatment with either the C-MOPP or BACOP combination chemotherapy regimens. Furthermore, 70% to 80% of these complete responders had long-term disease-free survival tan-tamount to cure. The third generation of NCI studies, termed the ProMACE-MOPP flexible induction program, significantly improved these results. Complete remissions were achieved in 74% of all patients and 73% of these remain disease free in excess of 3 years. Myelosuppression was dose limiting with a 10% septic death rate. Studies are currently underway in an attempt to minimize the toxicity of the new regimen, while preserving the increased complete response rates and long-term survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Vincristine

Methotrexate with leucovorin rescue (HDMTX-LV rescue), has been used to treat solid tumors and non-Hodgkin's lymphomas (NHL). We studied the use of HDMTX-LV rescue in patients with widespread NHL with histologic diagnosis of diffuse poorly differentiated lymphocytic and diffuse histiocytic including involvement of the central nervous system (CNS) and/or bone marrow. The prognosis with conventional chemotherapy is extremely poor. Three patients have bone marrow involvement, 2 patients CNS, and 2 both. These patients were unresponsive to conventional chemotherapy and had a rapid progression of their disease. Therapy with HDMTX-LV rescue induced responses in 5 patients: 2 patients achieved a complete remission and three a partial remission. Regression of CNS involvement was observed in 3 patients; bone marrow toxicity was not observed. Only 1 patient failed to respond. These data suggest that HDMTX-LV rescue may be useful as primary therapy in lymphoma patients with CNS and/or bone marrow involvement.

Topics: Adult; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged

Phase II-III trials of oral VP 16-213 (VP 16) were conducted in non-Hodgkin lymphoma (NHL) and small cell lung cancer (SCLC). Of 29 heavily pretreated patients (pts) with NHL treated VP 16 at a dose of 200 mg/d days 1-5 q 3w, there were 3 CRs and 6 PRs (CR + PR : 31%) lasting 16 (7-185) weeks. Of 19 pts with NHL in stages III-IV treated by a non-cross alternating regimen consisting of AVCP (ADM, VCR, CPM, PDN)/EMLP (VP 16, MTX, L-ASP PDN), there were 4 CRs (21%) and 14 PRs (74%) lasting a median duration of 4.5 months. A combination consisting of VCR. VP 16 and CPM (VEC) was administered to a total of 29 pts with SCLC. Nine out of 10 pts with LD and 10 out of 19 pts with ED were attained CR after 2 cycles of VEC and subsequent irradiation to primary tumor. A median survival time of CR (LD + ED) exceeded one year while that of PR was 7+ months. These results indicated that oral VP 16 has significant activity for NHL and SCLC and lack of cross resistance to conventional drugs used for NHL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cyclophosphamide; Doxorubicin; Drug Evaluation; Etoposide; Humans; Leucovorin; Lymphoma; Methotrexate; Podophyllotoxin; Prednisolone

Nine children in remission from hematologic malignancies received infusion of methotrexate (2,000-6,000 mg/m2) for 24 hours followed by citrovorum factor rescue (beginning 36 hours after the start of MTX infusion). Marrow cell kinetics of these patients were studied by flow cytometry with computer analysis. An accumulation of cells in the early-mid S phase and a decrease of cells in the G2/M phase were observed at 24-48 hours after exposure to MTX except for one infant case. By the 6th day after MTX infusion, the DNA histograms returned to pretreatment values. No kinetic perturbation was observed in the marrow cells of a 1-year, 5-month-old infant who showed high plasma MTX concentrations over the median values of the other eight children. These results show that profound but reversible changes are observed in marrow cell kinetics in most patients treated with our current high-dose MTX therapy with CF rescue and that a repeated course would be possible without cumulative marrow toxicity. More studies in young infants are needed to clarify the relationship between age and marrow toxicity of MTX so that treatment schedules with a higher therapeutic index can be designed.

Topics: Bone Marrow; Cell Cycle; Child; Child, Preschool; DNA, Neoplasm; Drug Administration Schedule; Drug Therapy, Combination; Female; Flow Cytometry; Humans; Infant; Infusions, Parenteral; Injections, Intravenous; Leucovorin; Leukemia, Lymphoid; Lymphoma; Male; Methotrexate

Between March 1974 and December 1983, 83 patients with diffuse histiocytic lymphoma (DHL) were treated with COMLA (cyclophosphamide 1.5 g/m2 day 1; Oncovin (Lilly, Indianapolis) 1.4 mg/m2 days 1, 8, and 15; and cytosine arabinoside 300 mg/m2 and methotrexate 120 mg/m2 days 22, 29, 36, 43, 50, 57, 64, and 71; and leucovorin 25 mg/m2 every six hours X 4, beginning 24 hours after methotrexate). For the purpose of analysis, patients were divided into two groups. Group 1 (n = 54) included patients age 65 or under who had received no prior curative radiotherapy or chemotherapy. Group 2 (n = 29) included all patients over age 65 and patients who had received prior curative radiation therapy or prior minimal chemotherapy. The median time of follow-up for all patients was 28 months. Group 1 included 11 stage II, ten stage III, and 33 stage IV patients. Of 48 evaluable patients in this group, 21 (44%) achieved a complete remission (CR), eight (17%) achieved a partial remission (PR), and 19 (40%) showed no response (NR). Median survival of CR patients was 114+ months, PR patients, 42 months, and NR patients, 13 months. Six CR patients relapsed. The median disease-free survival of CR patients was 108+ months. Group 2 included nine stage II, seven stage III, and 13 stage IV patients. Of 24 patients evaluable for response, eight (33%) achieved a CR, six (25%) achieved a PR, and ten (42%) showed no response. The median survival of CR patients was 114+ months, that of PR patients was 17 months, and that of NR patients, 9 months. Two CR patients relapsed. The median disease-free survival of CR patients had not been reached at 102 months. The regimen was well tolerated in most patients and toxicity was acceptable. We conclude that COMLA is a well tolerated outpatient chemotherapy regimen capable of inducing durable CRs in some patients with DHL. Results achieved with COMLA, however, are inferior to those of more aggressive treatment programs; thus, the use of COMLA as first-line therapy in DHL should be limited to those patients unable to tolerate a more aggressive treatment program.

Topics: Actuarial Analysis; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prognosis; Vincristine

Chemotherapeutic drug delivery can be enhanced by administering drugs into the internal carotid or vertebral artery circulation after osmotic opening of the blood-brain barrier (BBB). As evidence of the clinical implications of this technique, radiographic documentation of central nervous system (CNS) tumor regression was observed in three patients concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic blood-brain barrier opening. These three patients, one with metastatic carcinoma of the breast, one with glioblastoma, and one with primary CNS lymphoma, highlight the importance of drug delivery to CNS malignancies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood-Brain Barrier; Brain Neoplasms; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Combined Modality Therapy; Cyclophosphamide; Female; Glioma; Humans; Leucovorin; Lymphoma; Male; Mannitol; Methotrexate; Procarbazine; Tomography, X-Ray Computed; Water-Electrolyte Balance

A combination chemotherapy program using methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD), which resulted in a high complete response rate and prolonged disease-free survival in lymphomas of the unfavorable diffuse histiocytic and diffuse undifferentiated histopathologic subgroups, was administered to 44 patients with advanced favorable and intermediate-prognosis non-Hodgkin's lymphomas, including nodular lymphoma of the poorly differentiated lymphocytic, mixed, and histiocytic subtypes, and diffuse lymphoma of the poorly differentiated lymphocytic or mixed histologic subtypes. High-dose methotrexate (3 g/m2) was given on Day 14 between cycles of bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone, administered every 3 weeks for ten cycles. Leucovorin factor (10 mg/m2) was given iv 24 hours after the methotrexate infusion was completed, and was continued at 10 mg/m2 by mouth every 6 hours for 72 hours. Therapy was well-tolerated, with predictable myelosuppression in the majority of patients. The complete response rate was 57% (25 of 44 patients), including ten of 18 (56%) patients with nodular and 15 of 26 (58%) patients with diffuse lymphomas. Median overall follow-up among living patients is 65 months, 58 months for patients with nodular and 69 months for patients with diffuse histologic subgroups. Overall survival at 5 years was 64% for patients who achieved complete response, 32% for partial responders, and 0% for those patients who did not respond. Disease-free survival of complete responders was 43% at 5 years, with only one disease-related death noted after 36 months. The nodular and diffuse patient subgroups had similar overall and disease-free survivals. Although initial bone marrow involvement was documented in nine of 18 (50%) nodular patients and in 13 of 26 (50%) diffuse patients, CNS relapse occurred in only one complete and two partial responders. The prolonged disease-free survival observed after M-BACOD therapy demonstrates that durable responses can be achieved with intensive chemotherapy.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma; Methotrexate; Prednisone; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Diseases; Lymphoma; Male; Methotrexate; Pulmonary Fibrosis; Respiratory Distress Syndrome; Testicular Neoplasms; Vinblastine; Vincristine

A new combination chemotherapy program (M-BACOD) was administered to 101 patients with advanced diffuse histiocytic and diffuse undifferentiated lymphoma (DHL and DUL). High dose methotrexate (M) 3 g/m2 with leucovorin factor rescue was given on day 14 between cycles of bleomycin (B), adriamycin (A), cyclophosphamide (C), oncovin (O), and dexamethasone (D) administered every 3 weeks for 10 cycles. The complete remission rate (CR) was 72% in all 101 patients or 77% in 95 evaluable patients. The median follow-up is 3 yr 2 mo with one-third of CR patients followed beyond 4 yr. Twenty-six percent of CR patients have relapsed with a projected 5-yr survival rate of 80% (5-yr disease-free rate 65%). The overall survival of all 101 study patients reaches a plateau at 59% projected out to 5 yr. Patients with prior therapy had a significantly lower CR rate than those without prior treatment (p = 0.001); however, no other unfavorable prognostic characteristics could be identified. Relapse in the central nervous system CNS occurred in only 5.4% of CR patients. M-BACOD results in prolonged survival and possible cure in a high proportion of all patients with DHL and DUL.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Female; Follow-Up Studies; Humans; Leucovorin; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Prognosis; Vincristine

A new treatment program was developed in an attempt to increase the complete remission rate and survival of previously untreated patients with advanced stages of diffuse aggressive lymphomas. A flexible number of cycles of ProMACE chemotherapy (prednisone, methotrexate, doxorubicin, cyclophosphamide, and epipodophyllotoxin VP-16) was alternated with a flexible number of cycles of MOPP chemotherapy (mechlorethamine, vincristine sulfate, procarbazine, and prednisone), and finally late intensification with ProMACE therapy was given. The duration of each phase of treatment was determined by the patient's rate of tumor response. Complete remissions were achieved in 55 of 74 patients (74%) with a median duration of follow-up exceeding 2 1/2 years. Only ten of the complete responders (18%) have had relapse. The dose-limiting toxicity is myelosuppression, and eight patients (10%) died from sepsis. Median survival for all patients has not been reached but is predicted to exceed 4 years with 65% of patients alive at 4 years. Previously we achieved a 46% complete remission rate with 38% of all patients alive at 4 years; relapse-free survival beyond 2 years was tantamount to cure. Therefore, ProMACE-MOPP chemotherapy represents a substantial improvement in treating patients with diffuse aggressive lymphomas.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Etoposide; Female; Humans; Leucovorin; Leukopenia; Lymphoma; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Vincristine

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Erythema; Etoposide; Female; Humans; Leucovorin; Lymphoma; Methotrexate; Prednisone

High doses of methotrexate (MTX) and leucovorin (LCV) as a rescue treatment were applied to five patients with non-Hodgkin's lymphoma, refractory to standard combination chemotherapy. Two of 5 patients showed a complete remission, and 2 patients showed a partial remission. One patient with massive pleural effusion showed an improvement by the treatment without any severe side effect under monitoring and controlling the dose of MTX. However, the remission duration of the treatment was short; therefore, additive therapy was required of later. From these results we assumed that the high dose of MTX and LCV could be effective for malignant lymphoma being resistant to other combination therapies.

Topics: Adolescent; Adult; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged

Twenty patients with pulmonary complications associated with combination chemotherapy regimens containing bleomycin were studied to determine common patterns of pulmonary radiographic abnormalities. All patients were receiving bleomycin on one of two different regimens of combination chemotherapy. Ten patients with non-Hodgkin lymphoma received a relatively low dose (22-64 mg total) and 10 patients with testicular cancer received a higher dose (360 mg total). The high-dose group showed subclinical radiographic lung toxicity changes in eight (80%) patients during and after therapy. Chronic pulmonary abnormalities were seen in nine (90%) patients in the high-dose group but in only three (30%) patients in the low-dose group. These was no significant difference in the pattern and distribution of lung infiltrates in these two groups. Infiltrates involving mainly the costophrenic triangle were seen in 18 (90%) patients; in six (33%) of these the changes were confined to the costophrenic triangles bilaterally and nearly symmetrically. Five (25%) patients had infiltrates at the periphery of the lungs. Elevation of the diaphragm was seen in 16 (80%) patients. A pleural reaction without gross effusion was seen in nine (45%) patients, of whom five (55%) demonstrated thickening of the interlobar fissures. Chronic lung changes were mostly confined to the bases in the form of failure of reexpansion of the costophrenic triangle (55%), persistent elevation of the diaphragm (35%), and a reticular meshwork of fibrosis at the costophrenic triangles (25%). Minimal lung disease was manifest as ground glass appearance at the lung bases and as fine, linear or reticulonodular densities that involved the costophrenic triangles.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Exudates and Transudates; Humans; Leucovorin; Lung; Lymphoma; Male; Methotrexate; Middle Aged; Radiography; Testicular Neoplasms; Vinblastine; Vincristine

Cytogenetic and pathologic studies were performed on six patients with angioimmunoblastic lymphadenopathy (AILD). All six had diffuse lymphadenopathy; five had fever, four had weight loss, and four had a diffuse erythematous rash. All patients except one had a polyclonal elevation of immunoglobulin. All patients had diagnostic findings in lymph node (LN) and bone marrow (BM) biopsies. Two patients died of progressive AILD; one patient died after transformation of AILC to immunoblastic sarcoma (IBS); one patient died of gastrointestinal bleeding of unknown cause. The remaining two patients, who have achieved complete remission with intensive chemotherapy, are alive 20 and 8 mo after the diagnosis; one of these had AILD and the other, both AILD and IBS. Despite diagnostic BM biopsy findings, none of the patients had chromosome abnormalities in their BM cells. In studying LN cels of 5 patients, however, we found chromosome abnormalities in each; clonal abnormalities were detected in two, both clonal and nonclonal abnormalities in two, and only nonclonal single-cell abnormalities in one. An extra chromosome 3, seen in four patients, was clonal in two and nonclonal in the two others. Cells with +5, +15, +19, +21, +22 were seen in two patients. All patients had 50% or more normal dividing cells in their LN. The mosaicism of unrelated abnormal cells in their LN. The mosaicism of unrelated abnormal karyotypes that was seen in four patients suggests that this malignant tumor is not necessarily monoclonal in its early stages, but that one clone may be selected and predominate in the late stage. Because nonrandom acquired clonal chromosome abnormalities are a consistent feature of malignancies, our data suggest that AILD may be a malignant disease despite its original description as a benign proliferative process. Therefore, it may require aggressive chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chromosome Aberrations; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Female; Herpes Zoster; Humans; Immunoblastic Lymphadenopathy; Karyotyping; Leucovorin; Lymph Nodes; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Procarbazine; Vinblastine; Vincristine

Sixteen patients with resistant non-Hodgkin's lymphoma were treated with continuous infusions of vincristine (1-2 mg/m2 daily X 2 days) and bleomycin (0.25 mg/kg bolus dose, then 0.25 mg/kg/daily X 5 days). Responding patients received high dose methotrexate (1500 mg/m2) with citrovorum rescue on days 15, 22, 29, 36. Treatment cycles were repeated every six weeks in responding patients. The response frequency was 50% (three complete and five partial responses). Median response duration was 29 weeks. Major toxicity included stomatitis (63%) and leukopenia (44%). One episode each of possible hypersensitivity pneumonitis and paralytic ileus occurred. Continuous infusions of vincristine and bleomycin should be studied further in less critically ill patients.

Topics: Adult; Aged; Bleomycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Humans; Infusions, Parenteral; Leucovorin; Leukopenia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Stomatitis; Time Factors; Vincristine

A regimen consisting of two courses of methotrexate (MTX) with leucovorin rescue followed 1 week later by cyclophosphamide, vincristine, and prednisone (MTX-COP) was studied in ten patients with disseminated diffuse non-Hodgkin's lymphoma who had had no prior chemotherapy. A similar regimen with the addition of doxorubicin (MTX-CHOP) was used for patients who had had previous chemotherapy: 11 with diffuse non-Hodgkin's lymphoma and two with Hodgkin's disease. The response rate to initial MTX administration was 55%, and the clinical onset of effect was usually observed within 48 hours. Responses were observed in previously treated and untreated patients. The remission rate was 100% with both regimens. There were seven complete remissions with MTX-COP and six with MTX-CHOP. The median durations of remission were 23 and 13 months, respectively; median survival was not reached in either group. MTX was well-tolerated by both groups of patients without serious toxic effects. Overall, significantly more hematologic toxicity was observed in previously treated patients; however, no life-threatening toxic effects were observed in either group. The incorporation of MTX and other antimetabolites into schedules of chemotherapy for previously treated and untreated patients with non-Hodgkin's lymphoma is well tolerated and deserved further exploration.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adolescent; Adult; Aged; Drug Therapy, Combination; Female; Hodgkin Disease; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged

Topics: Acute Disease; Adolescent; Adult; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukemia; Lymphoma; Male; Methotrexate; Middle Aged

Forty years ago, nitrogen mustard was first used in the treatment of a group of six patients with neoplastic diseases, including lymphosarcoma and Hodgkin's disease at Yale University. Since then different kinds of chemotherapeutic agents have been discovered, which clinical efficacy was reviewed as a single agent and in combination. Especially over the past two decades, the management of malignant lymphoma has improved significantly with combination chemotherapy. Now there are several potentially curative regimens, such as MOPP therapy for Hodgkin's disease, and MOPP (or C-MOPP), CHOP (or HOP), BACOP and COMLA for diffuse histiocytic lymphoma. There are recent trends to include methotrexate in combination and to use two non-cross-resistant regimens alternatively (CVP/ABP, MOPP/ABVD) for improving complete remission rate and remission duration. Treatment for favorable histologies, and clinical features and treatment of adult T-cell leukemia lymphoma were also briefly reviewed.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Hodgkin Disease; Humans; Leucovorin; Lymphoma; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Vincristine

Nineteen patients with malignant lymphomas were treated with 52 courses of high dose methotrexate with leucovorin rescue (HDMTX-LCV): 17 non-Hodgkin's lymphoma (11 nodal primary, and 6 Waldeyer's ring), 1 Hodgkin's disease, and 1 Burkitt's lymphoma; 10 No prior chemotherapy, 9 prior chemotherapy; Median age 50 years (18-67); Sex M 13:F 6. MTX was given according to Frei III et al's regimen(1975). In brief, alkalinization of the urine was achieved by administration of NaHCO3 both by oral and by intravenous route. Hydration with at least 3 liters of fluid per day was maintained throughout each course. MTX was administered as a six-hour infusion at an initial dose of 0.5-1.0 g/m2 with gradual escalation to 3-5 g/m2. Thirty minutes before the infusion of MTX, 1.4 mg/m2 of vincristine (VCR) (maximum dose 2 mg) was given intravenously in each course. MTX levels were not monitored. The overall response rate was 63% with 7 partial responses and 5 complete responses. Five of 10 previously untreated patients and 7 of 9 patients with prior chemotherapy achieved an objective response. Our excellent result may be contributed in part by VCR. Although, in general, during this study HDMTX-LCV was well-tolerated, a 67 year-old male had severe and unpredictable toxicity which resulted in shock condition, leukopenia and thrombocytopenia. Accordingly, we feel that HDMTX-LCV is dangerous without monitoring plasma MTX level. In other side effects, peripheral neuropathy and constipation possibly due to VCR occurred especially in elderly patients.

Topics: Adolescent; Adult; Aged; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Infusions, Parenteral; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged

High-dose methotrexate (HDMTX) with citrovorum factor (CF) was used to treat non-Hodgkin's lymphomas either as a single agent in those patients who had previously failed to respond to conventional chemotherapy or in previously untreated patients in combination with bleomycin, Adriamycin, cytoxan, and vincristine. Twenty-five patients who had been previously treated and were refractory to cytotoxic chemotherapy were treated with HDMTX ranging between 1 and 7.5 g/m2 as an iv infusion over 20 to 40 minutes. CF rescue was begun at 24 hours and was maintained orally every 6 hours at 10 mg/m2 for a total of 72 hours. In instances where the 24-hour serum level of MTX was in excess of 1 X 10(-7) M, the dose of CF was increased to 100 mg/m2 every 3 hours until the serum MTX level fell into the appropriate range. Of the 25 patients, 13 (52%) responded. Response duration was brief, lasting a median of 2 months. Three patients had prolonged control lasting 13, 16, and 21 months respectively. Five of the six patients with central nervous system (CNS) involvement have demonstrated marked clearing of spinal fluid abnormalities and reversion of brain scans toward normal. Fifty-four previously untreated patients with diffuse histiocytic or undifferentiated lymphoma have been treated with combination chemotherapy including MTX given at the level of 3 g/m2 on day 14 of a cycle. Bleomycin, Adriamycin, cyclophosphamide, and vincristine are given on Day 1 of the cycle. Dexamethasone 6 mg/m2 is given orally on Days 1 through 5. The cycle is repeated on Day 21, and patients are treated with 10 such cycles for a total of 30 weeks. Of our 42 patients who are evaluable for response and who have completed chemotherapy, 33 (78%) achieved a complete remission (CR). A total of seven patients have relapsed. Only one patient in the CR group has relapsed in the CNS after the cessation of chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Prednisone; Vincristine

Topics: Adolescent; Child; Child, Preschool; Humans; Kidney; Leucovorin; Lymphoma; Methotrexate; Osteosarcoma; Risk

The liquid-chromatographic measurement of 5-methyltetrahydrofolate in biological fluids is described. The sensitivity of the spectrophotofluorometric detector used allows direct evaluation of basal concentrations of the compound in plasma. Because it is resolved from the other common folates and from methotrexate, the procedure is suitable for monitoring it in plasma of patients receiving high-dose therapy with methotrexate.

Topics: Adult; Animals; Chromatography, High Pressure Liquid; Dogs; Folic Acid; Humans; Leucovorin; Leukemia, Lymphoid; Lymphoma; Male; Middle Aged; Spectrophotometry, Ultraviolet; Tetrahydrofolates; Time Factors

Thirteen patients with primary and metastatic CNS tumors have been treated with methotrexate (MTX) using three different approaches: (a) high-dose MTX with leucovorin (LV) rescue; (b) high-dose MTX with carboxypeptidase (CPDG) rescue; and (c) intraventricular administration of low doses of MTX for extended periods (concentration X time [CXT]). Eleven patients had central nervous system (CNS) lymphoma (one primary, one patient had recurrent medulloblastoma, and another patient had metastatic breast carcinoma. All 13 patients received high-dose MTX-LV rescue, while 3 patients were subsequently given MTX-CPDG. One patient received MTX by all three modalities. In patients with CNS lymphomas, complete responses (45%) and partial responses (36%) produced CNS disease-free intervals ranging from 1 to 23+ months. Survival for the complete responders has thus far ranged from 2.5 to 35 months, while the partial responders survived from 3 to 5 months. Two patients failed to respond and survived 2.5 and 3 months. Responses were obtainable with high-dose MTX-CPDG in patients resistant to MTX-LV. One patient who became sensitized to CPDG subsequently responded to MTX by intraventricular CXT administration. Thus, MTX can be effectively administered to patients with CNS tumors by several different approaches.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Breast Neoplasms; Carboxypeptidases; Female; Humans; Injections, Intraventricular; Leucovorin; Lymphoma; Male; Medulloblastoma; Methotrexate; Middle Aged; Time Factors

Topics: Antineoplastic Agents; Asparaginase; Bleomycin; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Prognosis; Thioguanine; Vincristine

Seven patients with advanced cutaneous T-cell lymphomas were treated with a combination chemotherapy regimen of vincristine, doxorubicin (Adriamycin), bleomycin, methotrexate, leucovorin factor, 5-FU, and hydrocortisone. All patients had an objective response but only one had a complete clinical remission. Our results are compared to other regimens reported in the literature.

Topics: Adult; Aged; Antineoplastic Agents; Bleomycin; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Hydrocortisone; Leucovorin; Lymph Nodes; Lymphoma; Male; Methotrexate; Middle Aged; Skin Neoplasms; T-Lymphocytes; Vincristine

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.

Topics: Adult; Bone Marrow; Bone Neoplasms; Breast Neoplasms; Drug Administration Schedule; Female; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Humans; Kidney; Leucovorin; Lung Neoplasms; Lymphoma; Methotrexate; Neoplasms; Urogenital Neoplasms

A 67-year-old man with malignant lymphoma, nodular, poorly differentiated lymphocytic type, developed meningeal lymphomatosis. Repeated high-dose methotrexate-citrovorum factor treatment (1 g/m2 in 24 hours) rendered the patient free of disease. The administration of vincristine at 23 hours consistently increased the concentration of methotrexate in the cerebrospinal fluid 2.5-fold above baseline values.

Topics: Aged; Drug Interactions; Head and Neck Neoplasms; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Time Factors; Vincristine

Topics: Child; Drug Administration Schedule; Female; Head and Neck Neoplasms; Humans; Kinetics; Leucovorin; Lymphoma; Methotrexate; Neoplasm Staging

Topics: Adolescent; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Kinetics; Leucovorin; Leukemia, Lymphoid; Lymphoma; Male; Methotrexate

Topics: Adolescent; Child; Child, Preschool; Drug Administration Schedule; Humans; Infant; Leucovorin; Leukemia; Lymphoma; Methotrexate; Neuroblastoma

Urinary alkalinization with oral sodium bicarbonate has decreased the incidence of acute nephrotoxicity and subsequent myelotoxicity in 18 adults receiving high-dose methotrexate with calcium leucovorin rescue (MTX-LCV) weekly in doses of 1-7.5 g/m2. Close monitoring of 24-hour serum creatinine and MTX levels can predict patients at risk for serious toxicity. By a prompt (24-36 hours) increase in the LCV dose rate, hematologic and biochemical evidence of myelosuppression has been prevented. Kinetic parameters in serum and lumbar cerebrospinal fluid (CSF) were studied in two patients following iv injection of 3 and 7.5 g/m2 respectively. Lumbar CSF MTX concentrations greater than 1 muM are achieved. The half-life of MTX in the CSF (11.95 hours) is twice as long as the serum half-life. In the presence of carcinomatous meningitis, further delay in the clearance of MTX from the CSF was seen. With weekly MTX-LCV, there have been four objective responses in six patients with non-Hodgkin's lymphoma in CNS relapse, including complete regression in two. It is suggested that therapeutic concentrations can be achieved in the central nervous system following MTX-LCV.

Topics: Adult; Aged; Bone Marrow; Central Nervous System Diseases; Creatinine; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Kidney; Kinetics; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Urine

Eighty-six adults with malignant disease were given high doses of methotrexate with folinic acid rescue, with acceptable toxicity. Protocal violations in two cases led to death. The results of therapy in some diagnostic groups are encouraging.

Topics: Adult; Carcinoma, Squamous Cell; Drug Therapy, Combination; Head and Neck Neoplasms; Humans; Leucovorin; Lymphoma; Methotrexate; Neoplasms

Topics: Animals; Asparaginase; Breast Neoplasms; Carboxypeptidases; Child; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia; Lung Neoplasms; Lymphoma; Melanoma; Methotrexate; Neoplasms; Osteosarcoma; Tetrahydrofolates; Thymidine

Topics: Adult; Drug Combinations; Female; Humans; Leucovorin; Lymphoma; Male; Meningeal Neoplasms; Methotrexate; Middle Aged

Topics: Aminopterin; Antimetabolites; Biological Phenomena; Folic Acid; Folic Acid Antagonists; Leucovorin; Lymphoma