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At least 55 records · Page 3Linked to original sources
PubMed1980

Methotrexate with citrovorum factor rescue: reduced chemotherapy toxicity in the management of gestational trophoblastic neoplasms.

The comparative systemic toxicity of methotrexate (MTX) with citrovorum factor rescue (CF), MTX alone and actinomycin-D (Act-D) in the treatment of gestational trophoblastic neoplasms (GTN) was evaluated in the present study. Treatment with MTX-CF was associated with only a 4% incidence (1 of 25 patients) of hepatic and/or hematologic toxicity and total absence of either a generalized rash or marked alopecia. In contrast, both MTX alone and Act-D were associated with a 48% incidence (12 of 25 patients) of hepatic and/or hematologic toxicity. Actinomycin-D also induced a generalized rash and marked alopecia in 24% (6 of 25 patients) and 52% (13 of 25 patients) of the patients respectively. We found that MTX-CF is the least toxic single agent chemotherapeutic regimen in the management of GTN.

Bone Marrow↗
PubMedDate not supplied

A phase II study of combined adriamycin, L-PAM, and methotrexate with citrovorum factor rescue in advanced ovarian carcinomas.

In a phase II study of combined adriamycin, L-PAM, and methotrexate with citrovorum factor rescue, 14 of 15 patients with primary advanced or recurrent ovarian malignant tumors obtained an objective remission. In remission, all patients improved their quality of life. So far the median duration of remission is 5+ months for the complete responders and 7 months for the partial responders. Myelosuppression of varying severity occurred in 93% of the courses. The regimen proved highly effective, although toxic in some advanced patients.

Adult↗
PubMed1976

Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms.

Fifteen patients with nonmetastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor. Complete and sustained remission was achieved in 14 of the 15 patients. Response to treatment was determined solely on the basis of serial serum human chorionic gonadotropin levels as measured by the beta subunit radioimmunoassay. All patients developed nonmetastatic gestational trophoblastic neoplasms following evacuation of a molar pregnancy. The known histologic diagnosis in all cases was hydatidiform mole. No significant toxicity was encountered despite careful monitoring of marrow, hepatic, renal, neurologic, and mucocutaneous parameters. Up to January 31, 1976, duration of remission ranged from 2 to 14 months.

Adolescent↗
PubMed1985

Reduced citrovorum factor rescue for high-dose methotrexate therapy in childhood malignancies.

Clinical toxicities and pharmacokinetics of methotrexate (MTX), associated with reduced citrovorum factor (CF) neutralization, were studied on 279 infusions in 25 children with various malignancies. MTX, at 1000-8400 mg/m2, was infused during six to 24 hours with multiple schedules of reduced CF rescue. Plasma MTX levels ranged from 7.0 X 10(-5) to 7.0 X 10(-4) M during MTX infusion. The levels declined rapidly with a two-phase elimination pattern (t1/2 = 1.2-2.5 hours, t1/2 = 18-32 hours). The folate level in the plasma ranged from 5 X 10(-7) M to 1.4 X 10(-6) M when CF was administered every six hours or every three hours, respectively. Limited bone marrow suppression was seen in only seven percent of infusions, with moderate elevation of GOT and GPT in 20% of infusions, and stomatitis in only 2.6% of infusions, despite reduction in the total dose of CF from 225 mg to 105 mg and despite delaying CF initiation from nine hours to thirty-six hours after the start of MTX infusion.

Adolescent↗
PubMed1977

Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: pre-surgical treatment of primary tumor and of overt pulmonary metastases.

Vincristine-high-dose methotrexate-citrovorum factor (VCR-MTX-CF) was administered preoperatively at weekly intervals to eight patients, four with primary tumors and four with pulmonary metastases. These patients had not received prior VCR-MTX-CF treatment. A similar treatment program was administered to five patients with pulmonary metastases who had received prior VCR-MTX-CF. Among the eight patients who had not received prior VCR-MTX-CF, complete responses were obtained in three with primary tumors (this was followed by surgical excision) and two with pulmonary metastases. Partial responses occurred in two additional patients. Partial responses were also obtained in two patients who had received VCR-MTX-CF. Chemotherapy and surgery in one patient with an extremity lesion resulted in preservation of the limb and useful function. The major toxicity was anorexia and weight loss. Other side effects included stomatitis, myelosuppression, hepatitis and transient renal impairment. The weekly program was highly effective when compared to responses obtained with the tri-weekly schedule utilized in previous studies.

Bone Neoplasms↗
PubMed1993

[Methotrexate-citrovorum factor individualized reduced dose therapy for ectopic pregnancy: report of 20 cases].

In twenty patients with ectopic pregnancy who received treatment using methotrexate-citrovorum factor in an individualized reduced dose regimen 17 cases were successfully treated, 4 required one course of therapy, 8 required two courses, 4 required three courses, only 1 required four courses, according to the difference in the speed of hCG reduction. The success rate was 85.0%, two cases got intrauterine pregnancy within 6 months after the treatment. Three ruptured cases during treatment were operated upon. The pathologic findings at the ectopic site were chorionic bleeding, necroses, with dissolution of trophoblastic cells.

Adult↗
PubMed1979

Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms.

Fifty-one patients with nonmetastatic gestational trophoblastic neoplasms (NMGTN) were treated with either 4 or 6 mg/kg methotrexate (MTX) and citrovorum factor (CF) rescue to determine if the higher dosage could reduce the number of courses of chemotherapy required to achieve remission. Thirty-six of 41 patients treated with 4 mg/kg MTX achieved complete remission with 1 course of chemotherapy. Increasing the initial dose of MTX to 6 mg/kg in 10 patients did not reduce the need for subsequent courses of chemotherapy but did increase associated toxicity. The rate of fall in the human chorionic gonadotropin (hCG) titer following the initial course of MTX-CF was found to be an accurate predictor of therapeutic response. The need for further chemotherapy may be anticipated if the hCG titer has not fallen by 1 log within 18 days.

Adolescent↗
PubMed1989

[Treatment of gestational trophoblastic neoplasms with methotrexate and citrovorum factor rescue: analysis of 43 cases].

From Jan. 1979 to Nov. 1987, 38 patients with invasive mole and 5 patients of choriocarcinoma were primarily treated with methotrexate and citrovorum factor (MTX-CF) rescue. Thirty-two patients had non-metastatic disease (stage I) and 11 had metastatic disease (stage IIA in 5 cases, stage IIB in 3 cases and stage IIIA in 3 cases). Complete remission was achieved in 28 (87.5%) of 32 patients with non-metastatic disease and in 9 (81.8%) of 11 patients with metastatic disease. Six patients with MTX-CF resistant tumors subsequently achieved complete remission with intravenous infusion of KSM and/or AT 1258. All patients were followed up periodically, 22 of them have been followed up for over 2 years, the longest duration of follow-up being 7 years. Seven of the 14 patients with preserved uterus became pregnant after recovery. All children grew up normally.

Adult↗
PubMed1978

Methotrexate with citrovorum factor rescue for gestational trophoblastic neoplasms.

Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay.

Adolescent↗
PubMed1982

[Studies on the effect of high-dose methotrexate-citrovorum factor treatment for 89Sr induced osteosarcoma in mice (author's transl)].

We treated mice with 89Sr induced osteosarcoma with HD MTX (high-dose methotrexate) and CF (rescue by citrovorum factor), and observed the results of MTX administration. MTX and CF constantly injected through their tail veins at intervals of 6, 24 hours, respectively. The amont of MTX administered ranged from 60 mg/kg to 2,000 mg/kg, while CF administered totalled 200 mg/kg. To determine their antitumor efficacy, we adopted 3H-thymidine based labelling index and mitotic index as well as microautoradiography, and observed how the tumor proliferation had been prohibited. The anti-tumor efficacy was significant when 500 mg/kg of MTX was administered; there was no significant increase in anti-tumor efficacy even after 1,000, 2,000 mg/kg of MTX had been administered. Rather, the tumor was tending to be healed as time passed by after the administration of MTX being 500 mg/kg. Then we administered 500 mg/kg of MTX and 200 mg/kg of CF twice at intervals of 6 days. After we had administered MTX in combination with CF, we started observing the changing condition of the tumor. As a result, we recognized their significant anti-tumor efficacy. The tumor did not show any indication of serious growth. In view of the above, we concluded that it would be more effective to administer repeatedly an optimum dose of MTX and CF than to administer an ultra-high dose of MTX and CF.

Animals↗
PubMed1978

Treatment of mycosis fungoides lymphoma: effectiveness of infusions of methotrexate followed by oral citrovorum factor.

Eleven patients with stage II or III mycosis fungoides lymphoma were treated with a regimen consisting of iv infusions of methotrexate (MTX) (60-240 mg/m2) administered sequentially and oral citrovorum factor. All 11 patients experienced a good to excellent response. Complete remissions were induced in seven of the 11 patients. In most cases remissions were sustained with weekly administration of low-dose (25--50 mg) MTX. Adverse drug reactions, such as leukopenia, anemia, and mucositis, were minimal in degree. Some unique adverse reactions included skin ulcerations (three patients), a leukocytoclastic angiitis (one patient), and painful hands and feet during MTX infusions (two patients). Our experience with this regimen has led us to conclude that it is safe and very effective in the treatment of stages II and III of mycosis fungoides.

Administration, Oral↗
PubMed1983

Combination chemotherapy (high-dose methotrexate with citrovorum factor rescue, mechlorethamine, and procarbazine) in non-small cell lung cancer.

Twenty-five patients with non-small cell lung cancer (NSCLC) were treated with high-dose methotrexate with citrovorum factor resuce (HDMTX-CFR), mechlorethamine (HN2) and procarbazine (PCZ). Nineteen patients are evaluable for response. One patient had partial remission which lasted for 11 weeks. Nine patients had stable disease lasting for 6-22 weeks. HDMTX-CFR was well tolerated by these patients but this combination regimen produced very low tumor response rate (5.2%). Addition of HN2 and PCZ, chemotherapeutic agents active against NSCLC, failed to improve the tumor response rate but added to gastrointestinal and hematologic toxicity.

Adult↗
PubMed1978

Oral high-dose methotrexate with citrovorum factor rescue in metastastic squamous cell carcinoma of the lung.

Thirteen patients with metastatic squamous cell cancer of the lung were treated, in a nonrandomized study, with an oral high-dose methotrexate and citrovorum factor rescue regimen. There was some response and/or stabilization of disease for at least three months in six (46%) of 13 cases. The median survival time of the study group was double (365 vs. 180 days) that of a retrospectively matched control group. This suggests a possible therapeutic effect of this treatment program in metastatic squamous cell cancer of the lung.

Administration, Oral↗
PubMed1977

[Therapy of solid tumors using high-dose methotrexate and citrovorum factor].

Methotrexat (250-1100 mg/m2) was administered to 38 patients with malignant tumors by infusion of either 6 hours or of 75 minutes duration. MTX-infusion and continued at 3-6 hours interval for Citrovorum factor rescue was started 2 hours after 24 to 72 hours. 7 different MTX doses and rescue schedules were tested. It could be shown that MTX in the dose range used is effective in various tumors when CF-rescue is not higher than 7% of the administered MTX-dose, only occasionally therapeutic success was observed with higher doses. In the group of patients where CF-rescue was lower than 7% of the MTX dose on 9/14 patients objective tumor-regressions could be achieved. Conclusions drawn are discussed and the necessity of further investigations is emphasized.

Administration, Oral↗
PubMed1977

High-dose methotrexate with citrovorum factor rescue for the treatment of central nervous system tumors in children.

Eleven patients with brain tumors recurrent after surgery and radiation therapy were treated with high-dose methotrexate (MTX) (300-500 mg/kg) with citrovorum factor rescue (CFR). MTX was given as an iv infusion over 4 hours followed 2 hours later by oral CFR (10 mg every 6 hours X 12). MTX levels were measured in the serum, lumbar cerebrospinal fluid (CSF), and ventricular CSF at 0, 4, 12, 24, 48, and 72 hours from the start of the MTX infusion. MTX concentrations of greater than 10(-6) M were measured in the CSF over a period of 24 hours after the iv infusion. Peak CSF concentrations reached were greater than 10(-5) M. After the response to high-dose MTX with CFR was evaluated, vincristine (1.5 mg/m2) and a nitrosourea (methyl-CCNU or BCNU) were added to this treatment regimen. Two of four patients with recurrent pontine glioma and five of seven patients with recurrent medulloblastoma had favorable objective responses to treatment. It is suggested that high-dose MTX with CFR be cautiously considered for the primary treatment of intracranial neoplasms in children with the hope of increasing the cure rate for children with malignant brain tumors.

Brain Neoplasms↗
PubMed1985

[Studies on high-dose methotrexate with citrovorum factor rescue therapy in children: analysis of bone marrow cell kinetics by flow cytometry].

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.

Bone Marrow↗
PubMed1981

Marrow cell kinetics in patients treated with methotrexate and citrovorum factor.

Methotrexate (MTX) was administered by continual intravenous infusion for 24 hours in doses ranging from 200-800 mg/m2 to 16 patients who had metastatic cancers and normal bone marrows and 11 patients with acute leukemia. Citrovorum factor (CF) was administered every 6 hours for 12-15 doses beginning 36 hours after the start of the MTX infusion. Plasma and urine were collected to measure MTX concentration. Daily bone marrow aspirates were obtained for measuring intracellular MTX concentration, labelling index (LI), mitotic index (MI), grain count distribution, cellular DNA distribution by flow cytometry (FCM), and marrow morphology. The plasma MTX concentration proved to be a function of dose and creatinine clearance. There was a positive correlation between the creatinine clearance and MTX clearance. The intracellular MTX concentration correlated highly with the plasma concentration. The LI, grain count, and proportion of cells in S phase increased on days 2 and 3. The magnitude of the changes on days 2 and 3 was dose related. The MI fell on day 2 and recovered by day 4. Transient megaloblastic changes occurred. The cell cycle perturbations in leukemic marrow were less pronounced than those in normal marrows. These observations are consistent with a transient, dose related, S phase delay.

Acute Disease↗