Peripheral T-Cell Lymphomas Respond Well to Vincristine, Adriamycin, Cyclophosphamide, Prednisone and Etoposide (VACPE) and Have a Similar Outcome as High-Grade B-Cell Lymphomas

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T-cell malignancies including subentities with favourable (large cell anaplastic) or unfavourable (pleomorphic) prognosis. The clinical outcome of PTCL has been controversially discussed, but a worse prognosis than high-grade B-cell Non-Hodgkin's lymphomas (NHL) has been postulated by most authors. In this report we summarize the results of a prospective comparative study investigating the therapy outcome of 27 patients (pts) with PTCL and 55 pts. with high grade B-cell NHL and give an overview of therapy studies in PTCL. The histological sub-types were 14 pleomorphic, 8 large-cell anaplastic (Ki-1+), 2 angioimmunoblastic (AILD) and 3 other PTCL. In three patients the PTCL was associated with non-tropical sprue (11%). Nineteen patients presented with an advanced stage of disease (stage III and IV, 70%), 17 (63%) pts. had B-symptoms. The patients were treated with vincristine 2 mg dl, adriamycin 25 mg/m² dl-3, cyclophosphamide 800 mg/m² dl, prednisone 60 mglm² dl-7 and etoposide 120 mg/m² dl-3 (VACPE). In 77% of pts. with PTCL and 84% of patients with high-grade B-cell NHL a complete remission (CR) was achieved. 75% of the complete responders with PTCL and 70% with B-NHL are still in ongoing CR. The subgroup of large-cell anaplastic attained a CR in 88%. The median observation time is 44 months (1+-77+). The probability of 1-, 3- and 5-year overall and disease-free survival for the T-cell group were 76%, 54%, 48% and 76%, 62%, 62%, respectively according to Kaplan-Meier. There was no significant difference regarding the remission rate, the overall-, event-free or disease-free survival compared to high-grade B-cell lymphomas.

In conclusion, the VACPE regimen is an effective and feasible regimen in the management of PTCL achieving complete remissions in a large proportion of patients.     

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide,Vincristine, Doxorubicin,Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study

BackgroundWe retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen.Patients and MethodsPatients received up to 6 mEPOCH cycles. Etoposide (50 mg/m²/day), doxorubicin (10 mg/m²/day), and vincristine (0.4 mg/m²/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m²/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert’s formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6.ResultsIn 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation.ConclusionThe mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.     

Systemic Chemotherapy with Vincristine,Cyclophosphamide, Doxorubicin and Prednisolone Following Radiotherapy for Primary Central Nervous System Lymphoma: A Phase II Study

We treated 23 patients with primary central nervous system lymphoma with a protocol of conventional radiation up to 55±5Gy followed by 4 to 6 cycles of intravenous doxorubicin (30mg/m2), vincristine (1mg/m2) and cyclophosphamide (350mg/m2), and oral prednisolone (8–30mg/m2) (VEPA chemotherapy) repeated at 2-week intervals. The median age of the 23 patients was 59 years, and the median World Health Organization performance status score was 2. Seventeen patients received 4 or more courses of the chemotherapy, but 6 received only 1 or 2 courses for various reasons. The median survival time for all 23 patients was 25.5 months and their 5-year survival rate was 23%. These values were 34 months and 32%, respectively, for the 17 patients who received 4–6 courses of chemotherapy. After treatment, decline in performance status unaccompanied with tumor recurrence was observed in 44% of the patients; the incidence was apparently higher in older than in younger patients. The survival results obtained with this combined radiochemotherapy regimen appear to be better than those reported in most previous studies of patients treated with radiation alone. Post-irradiation VEPA chemotherapy appears to be worthy of further evaluation.     

Sequential Combination Chemotherapy of High-Grade Non-Hodgkin's Lymphoma with 5-Fluorouracil, Methotrexate, Cytosine-Arabinoside, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (F-MACHOP)

An intensive treatment program was developed to achieve durable remissions in a high proportion of previously untreated patients with advanced stages of diffuse high-grade non-Hodgkin's lymphoma (NHL). Fifty-six patients (15-68 years) received a course of F-MACHOP (5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone) every 3-4 weeks for 6 courses. Cycle active drugs were sequentially administered to expose rapidly proliferating tumor cells to the synergistic effects of these agents throughout the cell cycle. Forty-three patients achieved complete remission (77%) and 80% of the complete responders are projected to be alive and disease-free at 4'A years (median follow-up 33 months). Up to 70% of all patients are predicted to be alive at 5 years. Bulky tumor, “B”-symptoms and lymphoblastic histology were poor prognostic factors, particularly when associated with clinically detectable disease after three courses. Toxicity included transitory myelodepression in most patients (2 septic deaths). This protocol provides effective and tolerable therapy for the majority of patients with advanced stages of diffuse aggressive NHL.     

Combination Chemotherapy with Tegafur-Uracil (UFT), Etoposide, Adriamycin and Cisplatinum (UFT-EAP) for Advanced Gastric Cancer

Thirty-four patients with advanced gastric cancer were treatedwith combination chemotherapy employing Tegafur-Uracil (UFT),etoposide, Adriamycin, and Cisplatinum (CDDP) (UFT-EAP therapy).An objective partial response was obtained in 16 patients (47%)and the median duration of remission was 12.2 months. The 50%survival time for all 34 patients was 10 months. Patients withmoderately or well differentiated adenocarcinoma responded well(13/19, 68%), while those with undifferentiated adenocarcinomashowed a poor response (3/15, 20%). Six responding patientswere noted to have no evidence of viable cancer at the primarysite by endoscopic biopsy, and underwent gastrectomies. Theresected specimens showed complete disappearances of the primarytumors in four patients. The median survival time for the patientsreceiving gastrectomies was 24 months. The regimen was verywell tolerated, apart from moderate bone marrow suppression.Our results suggest that patients with advanced gastric cancercan be effectively treated with UFT-EAP chemotherapy     

Liposomal Daunorubicin (Daunoxome) in Combination with Cyclophosphamide, Vincristine and Prednisolone (COP-X) as Salvage Therapy in Poor-Prognosis Non-Hodgkins Lymphoma

We treated 33 patients with a variant of the standard 3 weekly CHOP regime, replacing doxorubicin with liposomal daunorubicin (DaunoXome, NeXstar Pharmaceuticals) 120 mg/m² (COP-X). Eighteen subjects had relapsed / refractory aggressive NHL and 15 had indolent NHL/CLL. Median number of courses received was 4 (1-8). Thirty-two patients were evaluable for efficacy and 26 (81%) responded. 88% of patients with aggressive NHL responded; three (18%) patients achieved complete remission (CR), 12 (70%) achieved partial remission (PR), 1 (6%) patient had stable disease (SD) and 1 (6%) patient progressed through treatment. Median duration of response for patients with aggressive NHL was 3 months. The response rate in indolent NHL/CLL was 73%. Four (27%) patients achieved CR, 7 (46%) PR and 4 (27%) SD. At two years post treatment, 55% of the patients with indolent NHL/CLL remain progression-free, although 4 patients have proceeded to consolidation therapy. Twenty-seven out of 28 (96%) patients developed neutropenia of short duration following one or more of their treatments. Twenty-three patients developed an infection at some stage during therapy (all associated with neutropenia) and required hospitalisation. There were two toxic deaths (infection) both of which occurred in patients who were neutropenic before starting COP-X. Platelet toxicity was mild in patients with normal platelet counts at the commencement of therapy. Alopecia and mucositis were mild. No clinical evidence of myocardial failure was observed. We conclude that the substitution of DaunoXome for doxorubicin in the CHOP regimen to form COP-X provides excellent efficacy against non-Hodgkin's lymphoma. Response durations were short but comparable to those reported with other regimes. COP-X was well tolerated with some suggestion of reduced non-haematological toxicity. The regimen should be considered as an alternative to CHOP with potentially less non-haematological toxicity, particularly cardiac; further studies are required to evaluate the regimen in this context.     

Major Prognostic Factors of Adult Patients with Advanced B-Cell Lymphoma Treated with Vincristine, Cyclophosphamide, Prednisone and Doxorubicin (VEPA) or VEPA plus Methotrexate (VEPA-M)

Eighty-two adult patients with advanced B-lymphoma, treatedbetween 1981 and 1983 with VEPA (vincristine, cyclophosphamide,prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate)in a prospective randomized fashion, were evaluated for pretreatmentcharacteristics. The overall complete response (CR) and the4-year survival rates were 74% and 45%, respectively. The relapserate was 51%. Stage of disease only was negatively associatedwith the CR rate in a multivariate analysis. The primary extranodaltumor site other than upper gastrointestinal (GI) tract andhigh grade pathology were found to affect disease-free survivaladversely in a Cox proportional hazards model. Poor performancestatus, advanced stage, primary extranodal tumor site otherthan upper GI tract, advanced age, high grade pathology andprior therapy by either surgery or radiation, were significantlyassociated with shortened survival in a Cox proportional hazardsmodel. These results indicate advanced B-lymphoma in Japan tobe generally similar to advanced non-Hodgkin's lymphoma in theWest in terms of prognostic factor characteristics, but theimportance of the primary site in predicting survival has notbeen reported in the West. Also, the lack of a survival plateauin patients with diffuse large cell lymphoma indicates moreintensive chemotherapy regimens than VEPA or VEPA-M to be needed.It was also found that the significant prognostic factors inpatients with advanced B-lymphoma were very different from thosewith T-lymphoma. The five factors: pathology, stage, primarysite, age, prior therapy by surgery or radiation, for whichthe risk ratio was more than 2.3, were used to construct a modelcontaining 23 categories of patients running an increasing riskof shortened survival; this divided patients into three groups.The CR and 4-year survival rates of low-, moderate- and high-riskgroups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively.The risk-grouping provides indications for determining optimaltherapy for individual patients and the need for new therapeutictrials in patients at high risk.     

Survival Analysis in Advanced Non Small Cell Lung Cancer Treated with Platinum Based Chemotherapy in Combination with Paclitaxel,Gemcitabine and Etoposide

Background: The wide spectrum of clinical features in advanced stages of non-small cell lung cancer(NSCLC) probably contributes to disparities in outcomes because of different prognostic variables significantfor stage IIIB/IV patients. Hence the aim of this study was to check for favorable response of patients to variouschemotherapeutic combinations with respect to patient survival in stage IIIB and stage IV NSCLC disease. Weselected those patients for our study who were receiving treatment with paclitaxel, gemcitabine or etoposide incombination with platinum based drugs. Materials and Methods: Seventy-two patients who visited the hospitalfrom June 2009 to November 2012 with confirmed diagnosis of lung cancer were included, and data were collectedfor follow up and classified according to treatment received with respect to patients’ regimen and response, andoverall survival. This study analyzed tumor variables that were associated with clinical outcome in advancedNSCLC patients who were undergoing first-line chemotherapy for stage IIIB/IV NSCLC. Results: Comparativedata on various parameters like age, gender, stage, histology, site of disease, metastatic site and chemo-regimenswas analyzed; these parameters predicted variable significant improvement for overall survival (p≥0.05). Oneand two year survival rates were 20.8% and 15.3% . Conclusions: In this study we found slight improvementin survival rates in NSCLC and clinical outcomes with one combination (carboplatin+paclitaxel). Overall therewere only marginal differences in survival rates for other chemo-regimens evaluated in this study.     

Intensive Chemotherapy with Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and Granulocyte Colony-stimulating Factor for Advanced Thymona or Thymic Cancer: Preliminary Results

A study was conducted to evaluate the impact of cisplatin, doxorubicin,cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulatingfactor (G-CSF) on advanced thymoma or thymic cancer. BetweenAugust 1989 and December 1994, 14 patients with invasive, metastaticor recurrent thymoma or thymic cancer were treated with cisplatin(80 mg/m², on day 1), doxorubicin (45 mg/m², on day 1), cyclophosphamide(800 mg/m², on day 1) and etoposide (80 mg/m², on day 1–3)with G-CSF (90 mg/m², on day 5–18) at the National CancerCenter Hospital, Tokyo. Courses were repeated every 3 or 4 weeksfor a maximum of 4 cycles. Twelve patients were treated with2 or more courses of PACE. Two patients were treated with onlyone course, one refused and another required emergency thoracicradiotherapy after one course of PACE. Six patients had partialresponses (3 thymomas and 3 thymic cancers) but there were nocomplete remissions (response rates, 42.9%; 95% confidence interval,17.7% to 71.1%). Moderate hematological toxicities were observed:grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopeniain 10, 13, 8 and 6 patients, respectively. Six patients developedinfections that required antibiotics. Surgical resection orthoracic radiotherapy after PACE treatment was performed in2 and 7 patients, respectively. The overall median survivaltime was 14.7 months (range, 5.9 to 59.7 months). For 9 patientswho had received no prior treatment before chemotherapy, themedian survival time was 8.9 months, and one patient survivedfor 4 years and is still alive. In conclusion, PACE with G-CSFfrequently produces objective remissions in patients with advancedthymoma or thymic cancer. A large-scale intergroup study isnecessary to determine the impact of this regimen on advancedthymoma and thymic cancer.     

Chemotherapy with vincristine (VCR) and etoposide (VP-16) in children with low-grade astrocytoma

Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m² for 7 to 8 weeks and VP-16100 mg/m² for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, l exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor. Vincristine and etoposide produced minimal hematological and neurological toxicity and appeared to offer some benefit in patients with LGA. The authors suggest the therapy potentially can produce prolonged disease stabilization, or perhaps help avoid irradiation in the young child with LGA.     

Combination Chemotherapy with Cyclophosphamide,Doxorubicin and Vincristine in the Treatment of Stage III-IV Small-Cell Lung Cancer

Summary

Twenty patients with histologically confirmed small-cell lung cancer were treated with cyclophosphamide 1000 mg/m² i.v. on day 1, vincristine 1.4 mg/m² i.v. day 1, and adriamycin 50 mg/m² i.v. on day 1. This protocol was repeated every 21 days. Out of 17 evaluable patients 2 obtained a complete response (12%) with a mean duration of 11 months, 4 patients achieved a partial response with a mean duration of 6.3 + months, and 1 had a minimal response of 7.2 months. Two patients had a stabilization which lasted a mean of 4 + months, while 8 patients progressed. Although the mean survival was higher in responders than in non-responders, the difference in survival time was not statistically significant. The treatment was quite well tolerated with hematological toxicity in 78% of cases, oral and gastrointestinal toxicity in 83%, alopecia in 78%, and neurotoxicity in 16% of cases.     

Adjuvant Chemotherapy for Invasive Urothelial Cancer: Experience with a Methotrexate, Vincristin, Cisplatin, Cyclophosphamide, Adriamycin and Bleomycin (MVP-CAB) Regimen: A Preliminary Report

MVP-CAB chemotherapy (methotrexate, vincristine, cisplatin,cyclophosphamide, adriamycin and bleomycin) was administeredto 28 patients with high grade, locally-invasive or regionallymph node- involved urothelial cancer as an adjuvant therapyafter radical surgery. The median follow-up period of all theevaluated patients was 24 (range, 5–62) months. The mediandisease-free durations in patients with pT1b+2+ 3 bladder andupper urothelial cancer were 26 and 22 months, respectively.In contrast, all patients with pT4 disease or lymph node metastaseshad a recurrence within 24 months of surgery. The median disease-freedurations in patients with pure transitional cell carcinoma(grade 3) of the bladder and upper urothelial cancer were 19and 18 months, respectively. The median disease-free durationin patients with grade 3 pT1b+2+3 pure transitional cell carcinomawas 19 months. In contrast, the median disease-free durationin bladder cancer patients with pT1b+2+3 squamous cell carcinomacomponents was 35 months. The three-year actuarial survivalrates were 79 and 89% for pT1b+2+3 bladder and upper urothelialcancer, respectively, while the three-year actuarial survivalrates of patients with pT4 bladder cancer and pT4 upper urothelialcancer were 0 and 100%, respectively. The two-year actuarialsurvivals in the bladder cancer and upper urothelial cancerpatients with lymph node involvement were 0 and 100%, respectively.The three-year actuarial survivals of patients with pure transitionalcell carcinoma (grade 3) were 53 and 80% in bladder cancer andupper urothelial cancer patients, respectively. The three-yearactuarial survival rate in patients with squamous cell carcinomaor adenocarcinoma components which did not recur was, however,100%. Although randomized studies comparing MVP-CAB and M-VAC(methotrexate, vinblastin, adriamycin and cisplatin) or otherchemotherapeutic regimens will be necessary, we believe ourresults indicate that MVP-CAB chemotherapy may be useful asan adjuvant therapy for patients with urothelial cancer, includingthose with squamous cell carcinoma and adenocarcinoma components.More intensive MVP-CAB chemotherapy, i.e., increasing the doseof cisplatin and giving at least five courses, as well as theuse of granulocyte colony stimulating factor and a new antiemeticdrug (granisetron), will, however, be necessary for patientswith pT4 or lymph node-involved disease.     

A Multicenter Trial of Infusional Etoposide,Doxorubicin, and Vincristine with Cyclophosphamide and Prednisone (EPOCH) in Patients with Relapsed Non-Hodgkin's Lymphoma

A phase II study was performed in a multicenter community setting of EPOCH (etoposide/doxorubicin/vincristine/cyclophosphamide/prednisone) chemotherapy in 93 patients with relapsed non-Hodgkin's lymphoma. Patients included 41 females and 52 males, ranging in age from 31-81 years (median, 63 years). Lymphoma histologies included diffuse large-cell (56), follicular (21), mantle cell (11), peripheral T-cell (3), and small lymphocytic (2) lymphomas. Patients had received a median of two previous chemotherapy combinations (range, 1-9). Most patients had received the drugs in EPOCH with their previous chemotherapy regimens (vincristine 97%, cyclophosphamide 97%, doxorubicin 87%, and etoposide 28%). A total of 350 cycles of EPOCH were administered. EPOCH chemotherapy gave a response rate of 51% in the entire cohort of 93 patients. Among the 83 evaluable patients, a response rate of 57% was observed (24% complete response, 33% partial response). Seven of the 47 responders remain in clinical remission at 3 years after EPOCH chemotherapy alone. Additionally, 11 patients are alive after further salvage chemotherapy (four patients) or bone marrow transplantation (seven patients). Myelosuppression was common, with 36% of all cycles resulting in an absolute neutrophil count nadir < 500/μL. This study confirms the activity of infusional chemotherapy with EPOCH in patients with relapsed non-Hodgkin's lymphoma.     

Concurrent Etoposide,Steroid, High-dose Ara-C and Platinum chemotherapy with radiation therapy in localised extranodal natural killer (NK)/T-cell lymphoma,nasal type

PurposeRadiation combined with chemotherapy has recently been proposed to treat patients with localised extranodal natural killer (NK)/T lymphoma (ENKTL), nasal type. However, the modalities of the chemoradiotherapy combination and drug choices remain a matter of debate. We conducted a concurrent chemoradiotherapy (CCRT) study with the ESHAP (Etoposide, Steroid, High-dose Ara-C and Platinum) regimen.MethodsAn induction phase with two upfront courses of CCRT delivering a 40 Gy dose of radiation concurrently with two cycles of the ESHAP chemotherapy regimen, followed by a consolidation phase with 2–3 cycles of ESHAP chemotherapy alone.ResultsThirteen patients with localised ENKTL nasal type were enrolled between January 2005 and December 2014. The median age was 62 years. Ten and three patients had Ann Arbor stage IE and IIE disease, respectively. They all completed the induction CCRT phase. A median of two consolidation ESHAP cycles were delivered. During consolidation, 8/13 (62%) patients had a reduction in the number of chemotherapy cycles or reduced chemotherapy doses, due to haematologically adverse events. The other five patients (38%) received the full number of ESHAP cycles of chemotherapy scheduled without a dose reduction. All but one patient (92%) experienced grade 3–4 haematological toxicity. The main non-haematological grade 3–4 toxicity was mucositis in 6/13 (46%) patients. All but one patient (92%) achieved a complete remission. Two-year overall survival was 72%.ConclusionsWith optimal management of the specific toxicities induced by this treatment modality, CCRT with the ESHAP regimen yielded high efficacy against localised ENKTL, nasal type.     

Advantage of Post-Radiotherapy Chemotherapy with CCNU,Procarbazine, and Vincristine (mPCV) Over Chemotherapy with VM-26 and CCNU for Malignant Gliomas

Between 1981 and 1987, 133 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with surgery and post-operative radiotherapy. 36 AA and 31 GBM patients were treated with adjuvant chemotherapy consisting of CCNU 100 mg/m² day 1, procarbazine 60 mg/m² days 1-14, and vincristine 1.4 mg/m² (max. 2 mg) days 1 and 8, every 6 weeks which we called a «modified PCV» (mPCV) regimen. 37 AA and 29 GBM patients were treated with adjuvant chemotherapy consisting of VM-26 75 mg/m² days 1 and 2, and CCNU 60 mg/m² days 3 and 4, every 6 weeks. Prognostic covariates such as patient’s age, Karnofsky performance status score and the extent of surgery were balanced between the two treatment groups. The time to tumor progression and survival time for both regimens show that mPCV produces a two-fold increase in these factors at the 50th and 25th percentile for AA patients, but not for GBM patients, although there are more long-term GBM survivors with mPCV than with the VM-26 + CCNU regimen.     

A Phase II Study on Lonidamine Combined with Cisplatin and Etoposide in the Treatment of Advanced Non-Small Cell Bronchogenic Carcinoma (NSCBC)

Summary

A group of 28 patients with advanced non-small cell bronchogenic carcinoma (NSCBC) entered a phase II study on cisplatin (60 mg/m², day 1) plus etoposide 120 mg/m², day 1 to 3), every 3 weeks, in combination with lonidamine (150 mg p.o. t.i.d. continuously from day 1). Seven out of twenty-seven (26%) evaluable patients obtained a partial remission (median duration 22 weeks, range 7-47). Although the side effects were mild, three patients stopped the therapy because of them. Median survival was 14 months, range 2-19. Further studies are necessary to clarify the role of «biochemical modulators» in NSCBC.     

Final Results of Cooperative Study of VEPA [Vincristine, Cyclophosphamide (Endoxan), Prednisolone and Adriamycin] Therapy in Advanced Adult Non-Hodgkin's Lymphoma: Relation Between T- or B-Cell Phenotype and Response

One hundred previously untreated adult patients with advancednon-Hodgkin's lymphomas were treated with VEPA (vincristine,cyclophosphamide, prednisolone and adriamycin in combination)therapy. The overall complete remission rate was 52%. The completeremission rate was markedly higher in the patients with lineage-undeterminedlymphomas (72.2%) as well as in the patients with B(non-T)-celllymphomas (58.5%) than in the patients with T-cell lymphomas(36.6%). The median duration of complete remission has not beenreached for lineage-undetermined lymphomas and most (77%) ofthe patients have been in remission for more than 2-yr, whilethe median duration of complete remission for B(non-T)-celltype was 16 mo with a 3-yr remission rate of 14%, and medianduration for the T-cell type was only 4 mo with a 2-yr remissionrate of 15% or less. Both complete remission and cell lineageof lymphomas markedly affected the survival period. Of the patientswho were not induced into complete remission, about 90% diedwithin 12 mo regardless of the cell lineage of the lymphoma,and their median survival was only 5–7 mo. On the otherhand, more than 90% of the patients with lineage-undeterminedlymphomas who were induced into complete remission are stillalive after 36 mo. Median survival was 37 mo and the 3-yr survivalrate was 56.1% in the case of B(non-T)-cell lymphoma with completeremission. Even in the T-cell lymphomas, significantly (a fewmonths) longer survival time will be expected in the patientsin complete remission. These facts indicate that complete remissioninduced by VEPA therapy contributes greatly to longer survivalof the patients, but its contribution is limited by the celllineage of the lymphoma. B(non-T)-cell lymphoma as well as lineage-undeterminedlymphoma responded well to VEPA therapy and some of the patientsmay be cured. On the other hand, T-cell lymphoma responded poorlyto VEPA therapy.     

Karyotypic Evolution in a Patient with a Preleukemic State of Adult T-cell Leukemia (Pre-ATL) progressing to Overt ATL

Karyotypic evolution in a 56-year-old male with a preleukemic state of adult T-cell leukemia (pre-ATL) that progressed to overt ATL is described. The patient was born in the Kagoshima district, an endemic ATL area in Japan. A clone with inv(14)(q11q32) which was not detected in a pre-ATL state appeared during the early phase of overt ATL. These findings suggest that inv(14)(q11q32) may have played an important role in leukemogenesis in the present case. Based on our cytogenetic data obtained from both the pre-ATL and overt ATL phases, a model of the leukemogenic process of ATL is proposed.