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Internal Medicine (Tokyo, Japan) 2015Despite the remarkable advances in chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), adult T-cell leukemia-lymphoma (ATL) is still associated...
OBJECTIVE
Despite the remarkable advances in chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), adult T-cell leukemia-lymphoma (ATL) is still associated with a high mortality rate. It is therefore essential to elucidate the current features of ATL.
METHODS
We retrospectively analyzed 81 patients with aggressive type ATL at our institution over a 7-year period based on Shimoyama's diagnostic criteria.
RESULTS
Eighty-one patients with a median age of 67.5 years were classified as having acute (n=47), lymphoma (n=32), or chronic type (n=2) ATL. They were initially treated by either palliative therapy (n=25) or systemic chemotherapy [n=56; cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy (n=25)/vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP)-doxorubicin, ranimustine, and prednisone (AMP)-vindesine, etoposide, carboplatin, and prednisone (VECP) therapy (VCAP-AMP-VECP) or CHOP-VMMV therapy (n=31)], and showed median survival durations of 16 and 277 days, respectively. Subsequent to the initial treatment, HSCT (n=6) was performed for certain patients, thus revealing that two-thirds (n=4) relapsed, and one-third (n=2) survived for 131 days and 203 days, respectively. The relapsed ATL patients were treated with conventional salvage therapy (n=29) or anti-CC chemokine receptor 4 antibody (mogamulizumab) (n=3). The patients treated with mogamulizumab demonstrated complete response (2) and partical response (1) with short duration periods of 82 days, 83 days, and 192 days, respectively. Among the five long-term survivors (>5 years) who received chemotherapy, most showed a low and intermediate risk according to the ATL prognostic index.
CONCLUSION
In our study, the overall survival of ATL remains poor due to the advanced age of the patients at diagnosis, a high proportion of patients receiving palliative therapy, and a small proportion of long-term survivors receiving chemotherapy and undergoing HSCT. This study illustrates the current clinical features, treatment strategies, and outcomes in clinical practice.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease Progression; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Prednisone; Prognosis; Remission Induction; Retrospective Studies; Survival Analysis; Treatment Outcome; Vincristine
PubMed: 26073237
DOI: 10.2169/internalmedicine.54.1953 -
British Journal of Cancer 1997The heterogeneity of therapeutic modalities and eligibility criteria and the lack of long-term follow-up in most reports of neoadjuvant chemotherapy for breast cancer...
The heterogeneity of therapeutic modalities and eligibility criteria and the lack of long-term follow-up in most reports of neoadjuvant chemotherapy for breast cancer preclude us from drawing conclusions about its value in clinically relevant patient subgroups. The present study aims to identify predictive and prognostic factors in 107 non-inflammatory stage II/III breast cancer patients treated between November 1980 and October 1991 with an anthracycline-based induction regimen before locoregional surgery. Preoperative chemotherapy comprised 3-6 cycles of doxorubicin (pirarubicin after 1986), vindesine, cyclophosphamide and 5-fluorouracil. Type of subsequent surgery and adjuvant treatment were decided individually. In analysis of outcome, univariate comparisons of end points were made using the log-rank test, and significant (P < or = 0.05) pre- and post-therapeutic factors were incorporated in a Cox multivariate analysis. With a median follow-up of 81 months (range 32-164+ months), the median disease-free survival (DFS) is 90.5 months while median overall survival has not yet been reached. Cytoprognostic grade and histopathological response in both the primary and lymph nodes were independent covariates associated with locoregional relapse with or without DFS and overall survival. Eleven patients with pathological complete response remain free of disease with a 68-month median follow-up, while the 18 with residual microscopic disease on the specimen showed a 60% cumulative incidence of locoregional recurrence. Despite encouraging response rates based on clinical or radiological evaluation (87% or 70%), neither method showed any significant correlation with pathological response and failed to contribute prognostic information on patients' outcome. Pathological evaluation of antitumoral activity of primary chemotherapy remains a major source of prognostic information and might be used to select patients in need of additional adjuvant treatment.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Humans; Lymph Nodes; Middle Aged; Neoplasm Staging; Postmenopause; Premenopause; Prognosis; Retrospective Studies; Survival Analysis; Vincristine
PubMed: 9155059
DOI: 10.1038/bjc.1997.230 -
British Journal of Cancer 1997The standard management of primary gastric lymphoma (PGL) (stage II) has not been established despite the use of various treatment modalities. The present prospective... (Clinical Trial)
Clinical Trial
The standard management of primary gastric lymphoma (PGL) (stage II) has not been established despite the use of various treatment modalities. The present prospective trial of combined surgery and chemotherapy for the treatment of PGL (stage II) included 25 consecutive patients treated between July 1978 and December 1993. Twenty-one patients were treated with total gastrectomy and four with partial gastrectomy; this was followed by post-operative chemotherapy with m-VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin), followed by consolidation chemotherapy with VEMP (vindesine, cyclophosphamide, methotrexate and prednisolone) or VQEP (vindesine, carbazilquinone, cyclophosphamide and prednisolone). Twenty-one of the 25 patients who completed post-operative chemotherapy were free of relapse 26-203 (median 94) months after the gastrectomy. Of the four patients who did not complete the projected chemotherapy, two relapsed and died of lymphoma. Another patient with recurrent lymphoma died in an accident, and the fourth patient was in remission at 54 months after surgery. The post-operative overall and disease-free survival rates at 10 years for the 25 evaluable patients were 81.6% and 92.0% respectively. Major surgical complications and treatment-related death after chemotherapy were not observed. PGL (stage II) appears to be curable when treated with gastrectomy and adjuvant chemotherapy.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carbazilquinone; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prednisolone; Prognosis; Prospective Studies; Stomach Neoplasms; Vincristine; Vindesine
PubMed: 9400946
DOI: 10.1038/bjc.1997.582 -
British Journal of Pharmacology Apr 19881. The uptake and retention of vincristine (VCR), vinblastine (VBL) and vindesine (VDS) were evaluated comparatively with respect to their cytotoxic action on a murine... (Comparative Study)
Comparative Study
1. The uptake and retention of vincristine (VCR), vinblastine (VBL) and vindesine (VDS) were evaluated comparatively with respect to their cytotoxic action on a murine lymphoblastic leukaemia (L5178Y). 2. The same parameters were measured on a derived subline of cells resistant to VCR (L5178Y/r) in order to determine whether the different degree of resistance to each alkaloid correlates with the amount of drug associated with the cells. 3. VCR was the most active on L5178Y cells (IC50 = 5.8 x 10(-9) M) while the activity of VBL and that of VDS were similar (IC50 4.4 x 10(-8) M and 3.5 x 10(-8) M, respectively). Nevertheless, a considerably larger amount of VBL was taken up by the cells compared to VDS, although there were no significant differences in their cytotoxic action. 4. The VCR resistant cell line also expressed resistance to VDS, whose IC50 was increased by a factor of 11.4, but not to VBL. However, the uptake and retention of the three alkaloids were similarly reduced in L5178Y/r cells regardless of the degree of resistance expressed. 5. Although a decreased drug uptake and/or retention by the cells provides an explanation for the resistance to vinca alkaloids, they do not seem to be the only factors accounting for the resistance shown by the cell line which we have isolated. 6. The results seem to indicate that part of the VBL taken up by the cells is not used to induce the cytotoxic effect, but is diverted to some cellular compartment(s) or rate controlling process(es) which are different from the target that mediates its cytotoxic action.
Topics: Animals; Body Water; Drug Resistance; Leukemia L5178; Leukemia, Experimental; Lymphocytes; Mice; Tumor Cells, Cultured; Vinblastine; Vinca Alkaloids; Vincristine; Vindesine
PubMed: 3390658
DOI: 10.1111/j.1476-5381.1988.tb11478.x -
Japanese Journal of Cancer Research :... Jul 1996Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and cisplatin (MVP) for inoperable stage III or IV non-small cell lung cancer in a randomized trial. Determinant factors for myelosuppression were evaluated by using univariate analysis and the logistic regression model. Recursive partitioning and amalgamation (RPA) was also used to define patient subgroups frequently suffering from severe bone marrow toxicity. Overall, 33 (25%) of 134 patients experienced at least one episode of grade 4 leukopenia. In univariate analysis, age, body surface area, serum creatinine, and pretreatment hemoglobin concentration were associated with severe leukopenia. A multivariate analysis using the logistic regression method showed that only raised creatinine level was an independent predictor for grade 4 leukopenia (P = 0.049). The RPA model generated three distinct subgroups based on age, body surface area and regimen. The three subgroups were distinguished by the frequency of severe (grade 4) leukopenia (50%, 25%, and 2.4%, respectively) (P < 0.001). Grade 4 leukopenia occurred more frequently in patients in class 3 (age > or = 65 years and treatment with MVP). The RPA model was useful in identifying the risk factors for myelosuppression induced by cisplatin-based chemotherapy, and in defining patient subgroups with elevated risk of toxicity.
Topics: Adult; Aged; Anemia; Antineoplastic Agents; Bone Marrow; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis
PubMed: 8698630
DOI: 10.1111/j.1349-7006.1996.tb00292.x -
British Journal of Cancer Oct 1986Lung tumours of non small cell pathology were cultured by clonogenic assay in several media. Culture was successful in spleen conditioned medium, but only 57% grew and...
Lung tumours of non small cell pathology were cultured by clonogenic assay in several media. Culture was successful in spleen conditioned medium, but only 57% grew and low plating efficiencies (PE) meant that only 23% of the original number produced significant drug results. Comparison of rat erythrocyte lysate (REL) medium with serum free defined medium (HITES) and HITES + 10% FBS demonstrated clear enhancement of PE in REL although growth was 100% successful in all these media. Ninety-three percent of samples tested against drugs in REL produced significant results. A later comparison of REL with McCoy's 5A + rbc +/- hydrocortisone produced relatively poor culture success for these 3 media and equivocal growth patterns. Low PE was attributed to age of rats used for rbc. Vindesine and cis-platinum cytotoxicity in spleen conditioned medium were 61% and 15% sensitivity respectively. These do not concur with clinical experience but the figures for overt resistance, at 39% and 69%, correspond with expected non-responders to these regimes. Drug testing in REL produced figures correlating more closely with clinical performance at 45% sensitivity to platinum and 36% of patients sensitive to both drugs, but the vindesine sensitivity at 55% is again discrepant with performance of this drug as a single agent.
Topics: Carcinoma, Non-Small-Cell Lung; Cell Survival; Cells, Cultured; Cisplatin; Colony-Forming Units Assay; Culture Media; Humans; Lung Neoplasms; Tumor Stem Cell Assay; Vindesine
PubMed: 3022779
DOI: 10.1038/bjc.1986.213 -
Annals of Oncology : Official Journal... Nov 2000Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multi-drug resistance (MDR) and to increase sensitivity to cytotoxic... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multi-drug resistance (MDR) and to increase sensitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgkin lymphoma. The value of VER for treating solid tumors is still a matter for debate.
PATIENTS AND METHODS
We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the clinical effect of oral VER given in association with chemotherapy. Instead of retreating patients with anthracycline, we used a partially noncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two cohorts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m2 i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). The other cohort (52 patients) received the same VDS and 5-FU treatment and an additional oral VER treatment (240 mg/day divided in 2 doses), from day 1 to day 28 of each cycle. Patients were treated until progression.
RESULTS
The treatment was well tolerated and no side effects that could be attributed to VER were detected. Patients treated with VER had longer overall survival (OS) (median OS: 323 vs. 209 days, P = 0.036) and a higher response rate (27% vs. 11%, P = 0.04) than those not given VER. Progression-free survival (PFS) was also longer but the difference was not statistically significant (median PFS: 4.6 and 2.7 months for the VER and non-VER groups respectively, P = 0.6).
CONCLUSIONS
This clinical trial demonstrates that a chemosensitizer, such as VER, can increase the survival of MBC patients with acquired anthracycline resistance.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Biological Transport; Breast Neoplasms; Calcium Channel Blockers; Cohort Studies; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Life Tables; Middle Aged; Neoplasm Proteins; Prospective Studies; Survival Analysis; Treatment Outcome; Verapamil; Vindesine
PubMed: 11142488
DOI: 10.1023/a:1026556119020 -
British Journal of Cancer Feb 1999Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping... (Clinical Trial)
Clinical Trial
Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m(-2) was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m(-2) was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3-4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3-4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9-36%). Median response duration was 31 weeks (range 11-83 weeks) and median survival time 31 weeks (range 2-171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity.
Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Quality of Life; Vindesine; Gemcitabine
PubMed: 10070884
DOI: 10.1038/sj.bjc.6690140 -
American Journal of Hematology Nov 2014Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen...
A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma. The GOELAMS LCP 99 trial.
Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m(2) (6-hr intravenous [IV]) and 3 mg/m(2) IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m(2) (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m(2) with doses ranging from 12-18 mg/m(2) IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m(2) . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m(2) . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Chemoradiotherapy; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Idarubicin; Immunocompetence; Infections; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neutropenia; Palliative Care; Prednisolone; Recurrence; Remission Induction; Renal Insufficiency; Thrombocytopenia; Treatment Outcome; Vindesine
PubMed: 25052698
DOI: 10.1002/ajh.23812 -
Annals of Oncology : Official Journal... Oct 1996To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.).
PURPOSE
To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer.
PATIENTS AND METHODS
204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat.
RESULTS
The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre.
CONCLUSIONS
In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.
Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Etoposide; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Middle Aged; Mitomycin; Multivariate Analysis; Survival Rate; Treatment Outcome; Vindesine
PubMed: 8922196
DOI: 10.1093/oxfordjournals.annonc.a010761