levoleucovorin and Pneumonia

Topics: Administration, Oral; Aged; Arthritis; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Leucovorin; Methotrexate; Oxygen Inhalation Therapy; Pneumonia; Treatment Outcome

Postoperative complications were investigated in 72 patients who received neoadjuvant therapy with esophagectomy. Preoperative chemotherapy consisted of 5-fluorouracil (700 mg/m2/day, on days 1 to 5), cisplatinum (70 mg/m2/day, on day 1) and leucovorin (20 mg/m2/day, on days 1 to 5). Preoperative chemoradiotherapy consisted of cisplatinum combined chemotherapy and radiotherapy (total dosage of 30-70 Gy). The incidence of postoperative pneumonia (16%) and anastomotic leakage (24%) in the preoperative chemotherapy group was slightly higher than that in the control group (n = 506), and mortality (6.0%) after esophagectomy in the preoperative chemotherapy group was higher than that (2.4%) of the control group. Postoperative morbidity and mortality were observed more frequently in patients who received two cycles of the chemotherapy than those receiving only one cycle. Postoperative complications occurred more frequently in patients suffering high grade toxicities due to the preoperative chemotherapy. The highest preoperative serum creatinine value correlated to that of postoperative period (r = 0.6494). The use of the preoperative chemoradiotherapy with a total exposure dosage of 60 Gy or more significantly increased the postoperative pneumonia rate (67%; p < 0.05) compared to the group receiving 40 Gy or less. The mortality rate (33%) also increased. The second cycle of the preoperative chemotherapy should be cancelled if patients suffer high grade toxicities during or after the first cycle, and the total exposure dosage of the preoperative chemoradiotherapy should be limited to 40 Gy or less.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Pneumonia; Postoperative Complications; Radiotherapy Dosage; Surgical Wound Infection; Survival Rate

We retrospectively studied 32 patients treated with the m-BACOD regimen in a single institution between January 1988 and December 1991. After four to seven courses, four patients presented severe acute pneumonitis (PaO2 < 55 mmHg in room air), with diffuse bilateral interstitial syndrome. Broncho-alveolar lavage displayed increased lymphocyte count (> 45%) with inversion of CD4/CD8 in two cases and no evidence of parasitic, bacterial or viral infection. All patients received methyl-prednisolone (0.5 to 1 mg/kg/d x 1 week) with both complete clinical and radiological recovery within a week. The m-BACOD regimen was continued without bleomycine for four patients and without bleomycine plus methotrexate for two patients, until the completion of eight courses, without recurrence of pneumonitis. Drug-exclusion decisions were made empirically because the exact nature of the pneumonitis was not recognized at the time of diagnostic. Because of the regular administration in the m-BACOD regimen, methotrexate leads to an increased risk of pneumonitis. We concluded that the use of the m-BACOD regimen should henceforth be discontinued.

Topics: Adult; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Methylprednisolone; Middle Aged; Oxygen Inhalation Therapy; Pneumonia; Vincristine

One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknown origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Toxicity was greatest in patients who were nonresponders to induction chemotherapy and such may have been related to the continued presence of advanced tumor. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Body Weight; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Head and Neck Neoplasms; Humans; Hypothyroidism; Leucovorin; Male; Methotrexate; Mucous Membrane; Osteoradionecrosis; Pneumonia; Radiotherapy; Time Factors; Ulcer

Fourteen patients with 16 metastatic ostogenic sarcoma lesions were treated with high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR), adriamycin, and pulse high-dose cyclophosphamide combined with radiation therapy. Thirteen of 16 lesions responded. Responses consisted of relief of pain (6/6 patients) in bone lesions, roentgenographic and clinical evidence of decrease in the size of the bone lesions (6/7 patients), and a decrease in the size of pulmonary metastases (2/4 patients). The 2 patients whose pulmonary metastases responded to combined therapy developed pulmonary fibrosis and pneumonitis in the treated areas 3 months after radiation therapy (RT) (1400 and 1600 rads respectively). Of two bulky primary tumors that appeared to respond, both were ultimately found to contain viable tumor; a third less bulky primary tumor appeared to respond more completely. Three smaller metastatic bone lesions that were ultimately biopsied showed no evidence of active tumor. It is concluded that: 1) combination therapy (particularly HDMTX and RT) has an additive effect in controlling osteogenic sarcoma bone lesions, but bulky primary tumors cannot be completely eradicated; 2) although synergistic in treating osteogenic sarcoma, combination therapy can produce enhanced toxicity in surrounding normal lung tissue; and 3) combination therapy is of value in the palliative treatment of metastatic lesions other than that of lung, and in the treatment of small primary bone lesions. However, experience to date does not justify the delay in surgical ablation of a primary lesion in a child who presents without metastatic disease.

Topics: Adolescent; Antineoplastic Agents; Child; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Pneumonia; Pulmonary Fibrosis; Spinal Cord Compression

Topics: Ampicillin; Bone Marrow Diseases; Child; Cloxacillin; Female; Humans; Inhalation; Injections, Intramuscular; Leucovorin; Leukemia, Lymphoid; Lung; Methotrexate; Pneumonia; Prednisone; Remission, Spontaneous; Vincristine

Sirotnak, F. M. (Sloan-Kettering Institute for Cancer Research, New York, N.Y.), Gloria J. Donati, and Dorris J. Hutchison. Folic acid derivatives synthesized during growth of Diplococcus pneumoniae. J. Bacteriol. 85:658-665. 1963.-Under cultural conditions permitting synthesis of folic acid in an amount greatly in excess (20- to 30-fold) of that required for maximal growth of Diplococcus pneumoniae, 85 to 90% of the growth factor accumulated as polyglutamates. Approximately equal amounts of mono- and diglutamates made up the remaining 10 to 15% found in culture material. Most of the polyglutamates occurred intracellularly, in a proportion of triglutamates to higher glutamates of about two to one. Only 10 to 15% of all folic acid derivatives (mono-, di-, and polyglutamates) found had folinic acid (5-formylfolate-H(4)) activity for Pediococcus cerevisiae. Practically all synthesis of the glutamyl-peptide moieties of folate seems to occur at an enzymatic step prior to folic acid, since no appreciable peptide formation occurred under conditions blocking folate synthesis. Sulfanilamide inhibition of growth by a block in folate synthesis was reversed by the addition of dihydrofolic acid, but not folic acid. The examination of two genetically distinct amethopterin-resistant mutant strains has revealed no gross differences in folate accumulation during growth when compared with the wild strain.

Topics: Antimetabolites; Folic Acid; Glutamates; Humans; Leucovorin; Metabolism; Methotrexate; Pediococcus; Pneumonia; Polyglutamic Acid; Streptococcus pneumoniae