levoleucovorin and Thymus-Neoplasms

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) and bulky disease in 10 (37%) patients. All were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 received more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year time to progression (TTP) and overall survival (OS) were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. Our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular type of lymphoma should now be evaluated in prospective randomized trials.

Topics: Actuarial Analysis; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Controlled Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Disease-Free Survival; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Methotrexate; Middle Aged; Prednisone; Procarbazine; Prognosis; Prospective Studies; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Remission Induction; Thymus Neoplasms; Treatment Outcome; Vincristine

Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients.. From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary.. T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081).. T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Child; Chromosomes, Human, Pair 17; Cisplatin; Combined Modality Therapy; Cyclophosphamide; DNA Topoisomerases, Type II; DNA-Binding Proteins; Doxorubicin; Female; Fluorouracil; Gene Amplification; Genes, erbB-2; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Leucovorin; Male; Middle Aged; Neoplasm Staging; Receptor, ErbB-2; Survival Rate; Thymus Neoplasms

Although aminopterin(AMN)-antibody drug conjugates have been demonstrated to have a greatly increased antitumor efficacy compared to the free drug, their use is limited by an increase in systemic toxicity manifested by weight loss and bone marrow suppression. Using a murine thymoma model (E3) in inbred mice, the toxicity of a sublethal dose of free AMN could be prevented by the administration of leucovorin 24 h following drug treatment, whilst maintaining the antitumour effect of the drug. The same rescue protocol completely abrogated the antitumour efficacy of AMN-antibody, although toxicity was also diminished. However, the later administration of leucovorin 48-72 h following a sublethal dose of AMN-antibody conjugates resulted in a maintenance of the anti-tumour efficacy of the immunoconjugates and a reduction in toxicity, with a mean percentage change in mouse weight not significantly different from that of the controls. These studies demonstrate that reversal of toxicity caused by AMN-antibody conjugates can be achieved by leucovorin while maintaining a powerful antitumour effect provided that the dose of leucovorin is administered 48-72 h after the conjugate.

Topics: Aminopterin; Animals; Antibodies, Monoclonal; Antigens, Ly; Immunotoxins; Leucovorin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Thymoma; Thymus Neoplasms