Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This manuscript reports the results of the first cooperative study on primary central nervous system lymphoma (PCNSL) in Japan. Of 196 patients registered, 170 were judged as having PCNSL. No patients were immunocompromised. Of the 170 patients with PCNSL, 93 were males and 77 were females. The mean was 56.7 years. One hundred and nineteen tumors were confirmed histopathologically, and 51 were diagnosed by neuroimaging alone. All the tumors were non-Hodgkin's lymphoma. According to the Working Formulation for Clinical Usage (WF), 96 out of 119 tumors were classifiable: 53 were diffuse large cell type (55.2%), 17 immunoblastic type (17.7%), 9 diffuse small cleaved type (9.4%), 6 diffuse mixed type (6.3%), 5 polymorphous type (5.2%), 5 small lymphocytic type (5.2%) and 1 small non-cleaved type (1.0%). Of 21 tumors studied immunohistochemically, 18 were B-cell type and 3 were T-cell type. Irradiated patients (144) survived significantly longer than non-irradiated patients, (median survival time, MST: 19.2 and 2.7 months, respectively; p < 0.001). There was a remarkable difference in survival among patients of the intermediate lymphomas; MST (18 months) of patients with large cell lymphoma was significantly shorter than MST (over 96 months) of patients with other intermediate grade lymphomas (small cleaved and mixed) (p < 0.001) and had no significant difference from MST (9 months) of patients with high grade lymphomas. If patients were irradiated with more than 40 Gy, higher doses and different modes of irradiation brought no further survival advantage. Chemotherapy was performed in 87 of 144 irradiated patients (60.4%). No regimens were effective in prolonging survival. Of 144 irradiated patients, a complete or partial response to initial treatment was demonstrated in 91 (63.2%) and 43 patients (29.9%), respectively. Improvement in performance status was confirmed in 82 patients (57.0%). Despite a good response to initial treatments, 88 out of 144 evaluatble patients have died of PCNSL (MST: 19 months). Multivariate analysis based on the Cox hazard model revealed that histology of tumor, age at onset, performance status, and radiotherapy were prognostic factors. Neither chemotherapy nor mode of surgery was a beneficial factor.
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PMID:Primary central nervous system lymphoma in Japan--a retrospective, co-operative study by CNS-Lymphoma Study Group in Japan. 780 71

We summarize here the antitumor activity of newly developed drugs against malignant lymphoma. Irinotecan hydrochloride (CPT-11) showed a CR rate of 15% and an excellent response (CR + PR) rate of 42% in patients with non-Hodgkin's lymphoma who had prior treatment. In patients with ATL, 13% achieved CR and a response rate was 39%. MST-16, a new orally administered bis(2, 6-dioxopiperazine) analogue, showed a CR of 3% and PR of 28% (response rate 31%), among patients with ATL, 9% of 23 patients achieved CR and the response rate was 44%. Phase I studies of fludarabine demonstrated a high response rate of 64%, especially in follicular lymphoma, with a number of patients achieving CR. Subsequent phase II studies demonstrated a response rate of 89% in patients with indolent lymphoma. KRN 8602 was developed in an attempt to improve the clinical efficacy of currently used anthracyclines. KRN 8602 has been shown to produce less cardiotoxicity and alopecia, yet has comparable antitumor effects to ADM, and also has demonstrated an antitumor effect on ADM-resistant tumors. CPT-11 and MST-16 were found effective not only in refractory non-Hodgkin's lymphoma, but also in patients with ATL, which had no standard therapy. Fludarabine has been demonstrated to be a very active drug in indolent lymphoid neoplasms, particularly CLL and low grade lymphoma. These new drugs are expected to overcome malignant lymphoma refractory to treatment thus far.
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PMID:[New antitumor drugs for malignant lymphoma: a review]. 803 Nov 56

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. 821 Feb 56

Irinotecan hydrochloride (CPT-11), topotecan, sobuzoxane, NC-190, and IST-622 are unique topoisomerase inhibitors and are investigational in Japan. CPT-11 is a water-soluble, semisynthetic derivative of camtothecin. CPT-11 shows its anticancer activity by inhibiting topoisomerase I activity, now a target of anticancer agents with major interest. Recent clinical trials reveal that CPT-11 is very effective in the treatment of cancer including lung cancer, cervical cancer, ovary cancer, stomach cancer, colon cancer, and non-Hodgkin's lymphoma. Major dose limiting toxicities are leukopenia and diarrhea, and are dose related. Topotecan is an another semisynthetic derivative of camtothecin and is also topoisomerase I inhibitor. Topotecan has undergone phase I clinical evaluations in USA, europe, and recently in Japan. DLF are leukopenia and neutropenia. Topotecan is more hydrophilic than its parent compound and shows lesser protein binding. Renal excretion appears to be the major route of elimination. Sobuzoxane (MST-16) is a unique derivative of dioxopiperazine, an inhibitor of topoisomerase II. In phase II studies, definite anticancer effects are observed in patients with non-Hodgkin's lymphoma and adult T-cell leukemia/lymphoma. Responses are seen even in pretreated cases. Leukopenia is also dose-limiting. Non-hematologic toxicities are mild and include alopecia and G.I. toxicities. NC-190 is a novel benzophenazine derivative with excellent antitumor activities against murine tumors. NC-190 also inhibits topoisomerase II. Now the drug is an early clinical phase II studies in Japan. Toxicities include bone marrow suppression, transient mild to moderate liver enzyme elevation, alopecia and mild G.I. toxicities. Tumor responses are occasionally encountered. IST-622 is a semisynthetic derivative of chartreusin. The drug is an inhibitor of topoisomerase II (and I in high concentration). IST-622 shows excellent, broad anticancer activity against murine tumors. The drug is well absorbed from small intestine. IST-622 is now in phase I clinical trial in Japan.
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PMID:[Topoisomerase inhibitors developing in Japan]. 842 86

It is known that the topoisomerase II inhibitors, MST-16 (sobuzoxane) and VP-16 (etoposide), are effective for the treatment of lymphoma. Five patients with refractory or relapsed non-Hodgkin's lymphoma (NHL) were treated with a combination of oral MST-16 and VP-16 over a long period. Two patients had severely refractory NHL. The remaining 3 patients could not be treated with intensive chemotherapy because of severe organ dysfunction or a poor hematopoietic reserve. All 5 are alive and well after MST-16 and VP-16 treatment. MST-16 and VP-16 are effective for NHL when intensive chemotherapy is ineffective or contraindicated.
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PMID:Long-term administration of oral low-dose topoisomerase II inhibitors, MST-16 and VP-16, for refractory or relapsed non-Hodgkin's lymphoma. 1115 89

A 55-year-old woman underwent breast-conserving surgery with irradiation for Stage IIB (T2 N1 M0) breast cancer of her right breast. Thereafter, she was treated orally with oral UFT and tamoxifen. Three years following surgery, she was diagnosed as having a non-Hodgkin's lymphoma. She underwent 6 cycles of EPOCH-G (etoposide, vincristine, adriamycin, cyclophosphamide, prednisolone, G-CSF) therapy, and obtained complete remission. Two years later, her neck and inguinal lymph nodes were swollen. Biopsy confirmed the relapse of NHL. She underwent salvage chemotherapies of MST-16, carboplatin, IVAC, and CPT-11, but the disease was refractory. In May 2000, bilateral pleural effusion was detected. Cytomorphologically, the pleural fluid specimen showed both atypical lymphoid cells and adenocarcinoma cells simultaneously. Existence of double cancer in the pleural effusion has not been reported, suggesting that this case is rare.
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PMID:[Simultaneous detection of both non-Hodgkin's lymphoma cells and breast cancer cells in pleural effusion--a case report]. 1458 90