levoleucovorin and Pulmonary-Fibrosis

Rapidly developing pulmonary fibrosis associated with the use of the anti-cancer drug oxaliplatin has been reported mainly by Asiatic literature as isolate case reports. This rare but potentially fatal side effect has neither identified risk factors nor established treatment guideline. We report here a new clinical case concerning a patient with advanced gastric cancer treated with the oxaliplatin-based FOLFOX regimen along with a review of the literature as well as a discussion of emerging experimental treatment mainly based on imatinib.

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzamides; Fluorouracil; Humans; Imatinib Mesylate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Piperazines; Protein Kinase Inhibitors; Pulmonary Fibrosis; Pyrimidines; Stomach Neoplasms

Interstitial lung disease in patients with colorectal cancer during chemotherapy combined with bevacizumab is rare.. We reviewed 104 colorectal cancer patients treated with standard chemotherapy with bevacizumab and examined the incidence of interstitial lung disease and its clinical features.. We identified interstitial lung disease in four patients (3.85%). All patients were male. The median age was 64.5 years. Three of four patients had a history of smoking; median smoking index was 40 pack-years. Except one patient who had asymptomatic pulmonary fibrosis, chest computed tomography before chemotherapy showed no fibrotic changes. Pulmonary function test before chemotherapy showed normal values. All patients had received median 10 cycles (range 10-15 cycles) of FOLFOX before the onset of interstitial lung disease. Interstitial lung disease developed during FOLFOX + bevacizumab in two patients and during FOLFIRI + bevacizumab in two patients. The initial symptom of interstitial lung disease was fever in all patients. The median duration from the last chemotherapy to the onset of interstitial lung disease was 3.5 days (range 2-8 days). Three of four patients showed Grade 3 or more severity of interstitial lung disease according to Common Terminology Criteria for Adverse Events v3.0. High-dose steroid therapy was effective in all patients.. Interstitial lung disease induced by standard chemotherapy with bevacizumab is rare, but rapidly progressed and were severe in our experience.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Alveolitis, Extrinsic Allergic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Disease-Free Survival; Fluorouracil; Humans; Japan; Leucovorin; Lung Diseases, Interstitial; Male; Medical Records Systems, Computerized; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Pulmonary Fibrosis; Retrospective Studies; Severity of Illness Index; Smoking; Tomography, X-Ray Computed

Oxaliplatin has been approved for adjuvant treatment of colorectal cancer. Toxicity induced by oxaliplatin is moderate and manageable, but some isolated cases of severe pulmonary toxicity associated to oxaliplatin have been reported. Two fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis are reported here.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Fatal Outcome; Female; Fluorouracil; Granulomatosis with Polyangiitis; Humans; Leucovorin; Lung Diseases, Interstitial; Lung Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Pneumonectomy; Postoperative Complications; Pulmonary Alveoli; Pulmonary Fibrosis; Respiratory Distress Syndrome; Sigmoid Neoplasms; Tomography, X-Ray Computed

Two cases of non-Hodgkin's lymphoma suffered from acute respiratory failure. Both patients were treated with MACOP-B therapy, and received recombinant granulocyte-colony stimulating factor (rG-CSF) during the myelosuppression. They had fever and severe hypoxemia several days after 11 and 12-week's treatment, respectively. The chest X-ray films revealed diffuse fine granular shadows in bilateral lung fields. The number of white blood cells had rapidly increased when the shadows appeared. These cases suggested the possibility that rG-CSF, or the rapid increase of white blood cells, might induce interstitial pneumonia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukocytosis; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Pulmonary Fibrosis; Recombinant Proteins; Vincristine

Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.

Topics: Acute Kidney Injury; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Enteritis; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Poisoning; Pulmonary Fibrosis

Topics: Antibodies, Monoclonal; Antiemetics; Antineoplastic Agents; Bleomycin; Free Radicals; Humans; Leucovorin; Liposomes; Methotrexate; Pulmonary Fibrosis

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

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