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At least 73 records · Page 4Linked to original sources
PubMed1985

Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma.

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

Adolescent↗
PubMed1981

Prolonged disease-free survival in advanced breast cancer treated with "super-CMF" adriamycin: an alternating regimen employing high-dose methotrexate with citrovorum factor rescue.

Sixty-six patients were treated with the combination "super-CMF" as follows: cyclophosphamide 100 mg/m2 po days 2 through 14; methotrexate 3.0 g/m2 iv days 1 and 8; 5-fluorouracil 600 m g/m2 iv days 1 and 8; citrovorum factor rescue 10 mg/m2 iv days 2 and 9 and po days 2 through 4 and 9 through 11; and Adriamycin 70 to 90 mg/m2 iv day 29. This cycle was repeated at 49-day intervals. The single-agent activity of high-dose methotrexate with rescue was first evaluated in breast cancer patients in a truncated phase II study; 3 of 19 had a partial response (greater than 50% regression of measurable lesions) after 2 to 6 weekly courses and another 6 to 19 had some objective evidence of response (greater than 25%, less than 50%). The response rate to the combination "super-CMF" was: complete response (CR) 15 of 55 evaluable patients (27%) and partial response (PR) 28 of 55 (51%). The median duration of response was 24.5 months and the median time to treatment failure was 21.6 months. Nineteen of these patients have completed 12 to 18 months of drug treatment and have been followed in continuing remission for 1 to 28 months without further therapy. The total response rate and the CR rate achieved with this regimen are substantial, and the durability of the responses appears to be considerably greater than that obtained with other drug combinations.

Adult↗
PubMed1991

Correlation of plasma methotrexate concentration with human chorionic gonadotropin and therapeutic response to low-dose methotrexate-citrovorum factor in low-medium-risk gestational trophoblastic tumors.

Seventeen patients with low- or medium-risk gestational trophoblastic tumors (GTT) and one patient with a placental-site trophoblastic tumor were treated according to an 8-day schedule of low-dose methotrexate (LDMTX) alternating with citrovorum factor (CF). Plasma concentrations of methotrexate (MTX) were correlated with serum human chorionic gonadotropin (hCG) levels and clinical response. After an intramuscular dose of 50 mg, plasma MTX levels rose rapidly, reached a peak concentration of 5.8 x 10(-6) M/liter at 1 hour and persisted above 10(-6) M/liter normally considered inhibitory for DNA synthesis, for approximately 7 1/2 hours. Rapid plasma clearance followed with plasma levels reaching 5-7 x 10(-8) M/liter at the time of CF administration. At 48 hours, plasma MTX levels continued to exceed 10(-8) M/liter--the break point for the appearance of clinical toxicity due to MTX. In six of sixteen, or 38%, an initial rise in hCG levels was observed. Five of the seventeen patients, or 29%, and the one patient with PSTT developed MTX resistance. The administered dose (approximately 30 mg/M2) and plasma pharmacokinetics did not differ significantly between the tumors that responded and became resistant to MTX. The authors conclude that MTX resistance in GTT occurs as a result of impaired cell membrane uptake, gene amplification of dihydrofolate reductase, or both.

Chorionic Gonadotropin↗
PubMed1977

Phase II study of combined vincristine, adriamycin, cyclophosphamide, and methotrexate with citrovorum factor factor rescue in metastatic breast cancer.

Fifty patients with metastatic breast cancer were treated with 8-day courses of vincristine (1 mg iv, Day 1), adriamycin (50 mg/m2 iv, Day 1), cyclophosphamide (100 mg/m2 orally, Days 1-8), methotrexate (200 mg iv by 3-hour infusion, Day 8), and citrovorum factor rescue (15 mg in 12, 18, and 24 hours after methotrexate, Day 8) at 3-4-week intervals. Forty-two patients had previously received treatment with hormones and 17 patients had received chemotherapy. Fifteen patients achieved a complete remission (CR) and 24 patients a partial remission (PR). There was a significant correlation between the response and the number of metastatic organs (0.01 less than P less than 0.02). The response rate was roughly uniform irrespective of the organ predominantly involved (0.2 less than P less than 0.3). The remission duration was significantly longer for the patients with CR compared with that for the patients with PR (0.001 less than P less than 0.01). The patients who achieved CRs and PRs survived significantly longer than the patients with no change and progressive disease (P less than 0.001). The toxic effects of the treatment were acceptable and no drug-related deaths occurred.

Adult↗
PubMed1980

Antineoplastic agents: high-dose methotrexate and citrovorum factor rescue.

Therapeutic drug monitoring procedures after moderate and high-dose methotrexate (MTX) therapy are reviewed. Serum levels of MTX along with creatinine clearance and weight loss can serve to identify patients at risk of serious hematological toxicity. Preventive measures to avert or reduce MTX toxicity include increased citrovorum factor rescue treatment, hydration, and alkalinization of the urine in order to increase the urinary clearance of MTX and prevent its precipitation in acidic urine. The toxicity of MTX is associated with a prolonged retention of the drug in the body. Since the initial clearance of MTX correlates well with endogenous creatinine clearance, only patients with normal renal functions are eligible for high-dose MTX therapy; however, MTX-induced renal toxicity may impair renal function during the course of therapy. Therefore, careful drug monitoring techniques are essential and have contributed to the effective use of high-dose MTX, although the potential of serious toxicity cannot be completely prevented. Further studies are needed to understand the complex mechanisms by which MTX exerts its toxic and therapeutic effects in cancer patients.

Dose-Response Relationship, Drug↗
PubMed2005

Combined chemotherapy with carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor for the treatment of aggressive non-Hodgkin lymphoma: a long-term follow-up study.

BACKGROUND: The standard treatment for patients with aggressive non-Hodgkin lymphoma (NHL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Since 1989, the authors have used a new chemotherapy regimen with combined carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor called BAVEC-MiMA. The objective of the current study was to explore, after a long follow-up period, the impact of this third-generation regimen for the treatment of aggressive NHL. METHODS: One hundred and one consecutive patients (median age, 41 years) with either B-cell (n=94 patients) or non-B-cell (n=7 patients), aggressive lymphoma were diagnosed and treated between 1989 and 1999 with the BAVEC-MiMA regimen. RESULTS: The complete response rate was 74%, and the overall response rate was 89%. Eleven patients with refractory disease died rapidly after a median period of 5 months. The major toxicity was Grade 4 neutropenia (according to World Health Organization criteria), which was observed in 15 patients (15%). There were four toxicity-related deaths. The overall survival rate was 63% at 9 years. In multivariate analysis, factors that were associated with advantage in overall survival were response to induction therapy, bulky disease, and high score on the International Prognostic Index (IPI). The disease-free survival rate was 77% at 9 years. In multivariate analysis, the IPI was the most important variable for the definition of disease-free survival. CONCLUSIONS: The BAVEC-MiMA regimen was feasible on an outpatient basis, it was tolerated well, and it showed a low toxicity-related mortality. The long follow-up in patients with NHL, which is a rapidly fatal disease, led the authors to observe that, with this regimen, a cure was obtained in > 50% of patients who had low-risk or low-to-intermediate-risk, aggressive NHL.

Adolescent↗
PubMed1990

Failure of single dose methotrexate followed by citrovorum factor in nonmetastatic gestational trophoblastic neoplasia.

With increasing cost of medical care, newer methods of administering chemotherapy on an outpatient basis are being sought to reduce the need for hospitalization and protracted losses of valuable time for patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). To achieve this end, two NMGTN patients were treated with a single course of one dose of methotrexate (MTX) followed by multidose Citrovorum Factor (CF) without observing the expected response. Failure to respond appeared to be due to the schedule of administration. Although the dose and plasma concentrations of MTX were considered to be adequate for cell kill, fractionation--as established by conventional schedules of MTX administration--appeared necessary for response by exposing the maximum number of trophoblastic cells to inhibitory levels of MTX during the S-phase of the cell cycle.

Adult↗
PubMed1982

Reversal by citrovorum factor of methotrexate-induced suppression of cell-mediated and humoral immune response in mouse model systems.

C3H/HeHa mice were immunized (day 0) with 5 X 10(8) sheep red blood cells (SRBC) or 3 X 10(7) EL-4 lymphoma cells (i.p.), and C57B1/6J mice were immunized (day 0) with 3 X 10(7) P815 mastocytoma cells (i.p.). Methotrexate (MTX, 100 mg/kg) was given i.p. on day +2, with or without citrovorum factor (CF) at equimolar dose. In the absence of CF in C57B1/6J mice, the complement-independent cellular cytotoxicity (CICC) response did not recover in 18 days from MTX suppression to levels seen in immunized controls, while in C3H mice, with EL-4 as antigen, the response equalled that of controls by day 18 and was similar to or greater than that of controls through day 28; in both cases the serum antibody response returned to control levels by day 20. In both mouse strains, CF produced immediate recovery of the responses measured. In contrast, with SRBC as antigen, while the MTX suppression of complement-dependent cellular cytotoxicity (CDCC) in the absence of CF recovered by day 7, the CICC response recovered much more slowly. CF administration produced a rapid (day 4) return of CDCC activity to control levels, but only a partial restoration of CICC activity by day 6. In conclusion, the kinetics of recovery of the CICC and CDCC responses and of CF rescue of MTX-induced immunosuppression were dependent on mouse strain and on immunogens used, as well as on the type of response measured. Thus, selectivity of MTX action is indicated.

Animals↗
PubMed1976

Methotrexate and citrovorum factor rescue in the management of childhood lymphosarcoma and reticulum cell sarcoma (non-Hodgkin's lymphomas): parolonged unmaintained remissions.

High doses of methotrexate (HDMTX), given in pulse infusions of 3 to 30 mg/kg body weight, were studied in 22 children with non-Hodgkin's lymphoma. Sixteen complete and five partial remissions were observed in 21 patients evaluable for remission induction. The dose of MTX was increased stepwise on consecutive treatments until objective tumor response occured. Citrovorum factor rescue (CFR) was used "on demand" when toxicity started to develop, and routinely after 30 mg/kg of MTX. Twelve patients who had no previous chemotherapy were entered in a Phase II study consisting of remission induction with HDMTX and remission maintenance with monthly HDMTX supplemented with one monthly injection of vincristine and Cytoxan and five days of oral 6-mercaptopurine and prednisone. Eleven patients achieved remissions (eight complete and three partial) with HDMTX and one with surgery and radiation followed by HDMTX. The three partial remissions improved to complete remission during remission maintenance. All 12 were given the maintenance cyclic combination chemotherapy. Seven of the 12 patients entered the unmaintained phase of the study. One patient relapsed 6 months after cessation of therapy and died 4 years after diagnosis. Six patients are alive and free of disease 2 1/2 to 5 1/2 years after discountinuing treatment and 4 1/2 to 8 1/3 years after diagnosis. Five of these six patients had advanced (Stage IV) disease.

Child↗