CN3OP: an active regimen in patients with relapsed/refractory Hodgkin's lymphoma

Patients with recurrent or refractory Hodgkin's and non-Hodgkin's lymphoma are increasingly being treated with high-dose therapy and hematopoietic cell transplantation. As minimal disease status at the time of transplant has been a repeatedly proven significant prognostic factor for long-term survival, effective initial cytoreduction is an important step in the process. Modern chemotherapy programs for Hodgkin's lymphoma include virtually all active agents and little is left for effective salvage. Mitoxantrone is an active agent in lymphoma that is not generally used in first-line treatment. The aim of this study was to determine toxicity and response rate to CN3OP (fractionated mitoxantrone 6 mg/m² on days 1,2 and 3, combined with standard dose cyclophosphamide, vincristine, and prednisone) in 44 patients with relapsed or refractory lymphoma., Most of patients had advanced disease and one or more extranodal sites at relapse. Median response duration to immediate past therapy was four months, and one third of patients had not responded to prior treatment. A median of 4 cycles of CN3OP were given per patient for a total of 173 cycles. Grade III–IV neutropenia occured in 53% of cycles, Grade I–III mucositis in 24%, and Grade I–III infection in 17% of cycles. of 34 evaluable patients with Hodgkin's lymphoma 12 (35%) achieved complete remission (CR) and 15 (44%) partial remission (PR) for an overall response rate of 79%. Two of five evaluable non-Hodgkin's lymphoma patients responded with PR. Median overall survival and event free survival in the entire group was 29 months and 11 months respectively. At this time 16 patients have died; 12 of lymphoma, two of unknown cause and two of other causes. Complete response to CN3OP correlated with survival. CN3OP is an effective and safe regimen for cytoreduction in Hodgkin's lymphoma patients pretreated with doxorubicin/alkylator/etoposide-containing primary therapies.     

Mesna/Ifosfamide, Mitoxantrone, Etoposide, Bleomycin, Vincristine, Prednisone (Mine-Bop) Combination Chemotherapy In The Treatment Of Refractory And Relapsed Non-Hodgkin'S Lymphoma

Twenty-one consecutive patients with refractory or relapsed non-Hodgkin's lymphomas were treated with a novel combination chemotherapy (MINE-BOP), comprising myelosuppressive (ifosfamide, mitoxantrone, etoposide) and non-myelosupressive (bleomycin, vincristine and prednisone) drugs. Median age of the patients was 42 years and all had intermediate or high-grade lymphoma. Fifteen patients had refractory disease. All patients had previously been treated with one or two regimens, containing anthracyclines. In all cases the duration between the last chemotherapy and the MINE-BOP regimen was shorter than 12 months. Response rate was 57% with 33% complete remission (CR). Median disease-free and overall survivals were 7 and 10 months respectively. The serum LDH level was the only significant prognostic factor in this study. The toxicity of this regimen was moderate with 24% of febrile neutropenia and 9% of microscopic hematuria. Toxic death due to febrile neutropenia was observed in one patient who had bone marrow involvement. To conclude, the addition of non-myelosuppressive drugs to the chemotherapy regimen and shortening the interval between the application of cytotoxic drugs as used in the present study did not show any improvement of response and survival in this group of patients.     

BACOD方案治疗复发及难治性非霍奇金淋巴瘤的临床研究

 目的　观察BACOD方案治疗复发及难治性非霍奇金淋巴瘤（NHL）的疗效及患者不良反应。方法　65例复发及难治性NHL患者,采用BACOD方案进行化疗,具体为：博莱霉素10 mg／m2,静脉滴注,第2、9天;环磷酰胺750 mg／m2,静脉滴注,第1天;长春地辛3 mg／m2,静脉注射,第1、8天;阿糖胞苷150 mg／m2,静脉滴注,第2天至第5天;地塞米松10 mg／m2,静脉滴注,第1天至第7天,3周为1个疗程。结果　完全缓解18例,部分缓解30例,稳定13例,进展4例,有效率70.8 %。有效患者中位缓解时间 10个月（2～35个月）。1年生存率32.3 %,2年生存率24.6 %。患者主要不良反应为骨髓抑制。结论　BACOD方案可作为复发及难治性NHL的解救方案。     

ACES方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的 应用阿糖胞苷(Ara-c)、顺铂(cisplatin)、足叶乙甙(etoposide),类固醇激素(storid)联合化疗治疗难治性或复发性非霍奇金淋巴瘤(NHL),观察疗效及毒副反应.方法 12例难治性或复发性NHL,给予Ara-c 500 mg,d5,顺铂40 mg,d1-3,足叶乙甙(VP16-213)100 mg,d1-4,Dex 40 mg,d1-5联合化疗.结果 总有效率(CR PR)为66.6%.毒副反应主要是骨髓抑制,经G-CSF治疗均可恢复.结论 与NHL经典方案无交叉耐药的ACES补救方案是治疗难治性或复发性非霍奇金淋巴瘤有效、安全的治疗方案.     

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease and non-Hodgkin's lymphoma. The Swedish Lymphoma Study Group

One hundred and three patients with recurrent or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) were retrospectively studied. Thirty-seven of the 44 patients with HD, 34/47 with high-grade malignant and 9/12 with low-grade malignant NHL were evaluable for response. Of the 37 evaluable patients with HD, 16 (43%) achieved complete remission (CR) and 4 partial remission (PR), giving a total response rate of 54%. Of the 34 evaluable patients with high-grade NHL, 5 achieved CR and 8 PR, giving a response rate of 38%. Of 9 evaluable patients with low-grade NHL, 2 achieved CR. The main toxicity was leukopenia, thrombocytopenia and infections. Twenty-six per cent of the patients developed septicaemia, which was fatal in 6 cases (6%). We conclude that MIME as salvage regimen can induce complete remissions in lymphoma patients, particularly in HD with previous heavy treatment, and that it is relatively well tolerated.     

CHOP with high dose cyclophosphamide consolidation versus CHOP alone as initial therapy for advanced stage,indolent non-Hodgkin's lymphomas

The role of high dose therapy, including autologous stem cell transplantation (ASCT) in indolent non-Hodgkin's lymphomas remains controversial. We evaluated a dose intense regimen of CHOP induction followed by high dose cyclophosphamide consolidation (CHOP-HC) versus CHOP alone in a prospective comparison to assess intensified therapy without ASCT. Twenty-five patients with previously untreated advanced stage indolent NHL were enrolled: follicular lymphoma, grade 1 (11 patients) and grade 2 (8 patients); small lymphocytic lymphoma (5 patients); and lymphoplasmacytic lymphoma (1 patient). All patients were treated as clinically indicated. The median age was 47 years (21-70). There were 15 males, and 10 females. Three patients had intra-abdominal stage II, 2 patients with stage III, and 20 patients with stage IV disease. All patients received induction with CHOP for 4 cycles (weeks 1,4,7,10): cyclophosphamide 750 mg/m 2 IV, doxorubicin 50 mg/m 2 IV, vincristine 1.4 mg/m 2 IV (2 mg capped dose) and prednisone 100 mg PO ×5 days. Following induction, responding patients were given consolidation with either high dose cyclophosphamide @ 3 gm/m 2 IV for 3 doses with G-CSF (weeks 13,15,17) or 2 additional cycles of CHOP (weeks 13,16), stratified by stage and bulk of disease. The overall response rate to CHOP was 92% (3 CR, 8 PR) and to CHOP-HC was 93% (4 CR, 8 PR). The overall response, complete response and partial response rates were comparable in both arms. Median progression free survival for CHOP was 15.9 and 23.0 months for CHOP-HC. At 74.3 months median follow-up, all patients in the CHOP arm have recurred; 3 patients in the CHOP-HC arm (3 CR) have not recurred. The median overall survival has not been reached (at 5 years, 77% OS for CHOP-HC versus 83% OS for CHOP alone]. Greater hematologic toxicity was observed with CHOP-HC resulting in an increased number of hospitalizations for sepsis. There were no treatment-related deaths. No myelodysplasia or acute leukemia has been seen to date. With no obvious improvement in CR and with greater hematologic toxicity than CHOP, CHOP-HC is not recommended for treatment of indolent non-Hodgkin's lymphomas.     

Phase III Trial of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (Chop) Versus Cisplatin, Etoposide, Bleomycin and Prednisone (CisEBP) for the Treatment of Advanced Non-Hodgkin's Lymphoma of High Grade Malignancy

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophos-phamide, doxorubicin, vincristine, prednisone) or CisEBP (cis-platin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocy-topenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.     

Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas

Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory indolent lymphoid malignancies.     

R-GemOx与RICE方案二线治疗复发或难治性弥漫大B细胞淋巴瘤的临床对比研究

对比美罗华联合奥沙利铂和吉西他滨（R-GemOx）与RICE方案二线治疗复发或难治性的弥漫大B细胞淋巴瘤（DLBCL）的疗效及毒副作用。方法:选取复发或难治性弥漫大B细胞淋巴瘤患者65例,随机分为两组,分别接受R-GemOx方案和RICE方案化疗。R-GemOx组方案为:美罗华,375 mg/m2静脉滴注,d0,吉西他滨（GEM）1 000 mg/m2,静脉滴注,d1、8;奥沙利铂（L-OHP）130 mg/m2,静脉滴注,d1;21天为1周期。RICE组方案为:美罗华,375 mg/m2,静脉滴注,d0;异环磷酰胺（IFO?）1 g/m2,静脉滴注,d1～d3;Mesna解救400mg,静脉滴注q8h,d1～d3;卡铂（CBP）,AUC=5,静脉滴注,d2;依托泊苷（VP-16?）100mg/m2,静脉滴注,d1～d3。21天为1个周期。每2周期进行疗效及毒性评价。结果:65例患者中,R-GemOx方案组,完全缓解（CR）4例（12.5%）,部分缓解（PR）17例（53.1%）,稳定（SD）6例,进展（PD）5例,总有效率（CR+PR）为65.6%,临床获益率（CR+PR+SD）达到84.4%。RICE组CR 4例（12.1%）,PR 16例（48.5%）,SD 7例,PD 6例,总有效率60.6%,临床获益率81.8%。两组的不良反应主要为骨髓抑制,其中R-GemOx组白细胞下降Ⅲ度5例,Ⅳ度2例;贫血Ⅲ度2例;血小板下降Ⅲ度4例,Ⅳ度2例。RICE组白细胞下降Ⅲ度16例,Ⅳ度5例;贫血Ⅲ度2例;血小板下降Ⅲ度5例,Ⅳ度3例。胃肠道反应RICE组较R-GemOx组为重,其中Ⅲ度2例,Ⅳ度1例。比较两组毒副反应,R-GemOx组在中性粒细胞减少,消化道反应方面明显好于RICE组（P<0.05）。而RICE组未出现一例末梢神经毒性。结论:R-GemOx方案是二线治疗复发或难治性弥漫大B细胞淋巴瘤较为安全且有效的化疗方案,其远期疗效尚需进一步观察。      

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).     

氟达拉滨为主的联合化疗方案治疗低度恶性非霍奇金淋巴瘤的临床观察

目的评价以氟达拉滨为主的化疗方案治疗低度恶性淋巴瘤的疗效和不良反应。方法采用氟达拉滨为主的化疗方案(FMD方案:氟达拉滨 米托蒽醌 地塞米松;FMC方案:氟达拉滨 米托蒽醌 环磷酰胺;FC方案:氟达拉滨 环磷酰胺)治疗我院收治的低度恶性非霍奇金淋巴瘤患者32例,其中初发19例,复发、难治13例。结果32例患者平均完成了4.1个疗程,完全缓解(CR)率为65.6%,部分缓解(PR)率为18.8%,总的有效(OR)率为84.4%。初发组CR率71.4%, PR率21.0%,OR率92.4%;复发、难治组CR率46.2%,PR率13.1%,OR率59.3%,两组CR率和OR率差异无统计学意义(P>0.05)。主要不良反应为骨髓抑制和免疫功能抑制。31.3%(10/32)的患者出现Ⅲ～Ⅳ级粒细胞减少,9.4%(3/32)的患者出现Ⅲ～Ⅳ级血小板减少。有7例患者出现感染、发热,其中2例肺部感染患者死亡。非血液学毒性主要为胃肠道反应及轻度的肝肾功能损害。中位随访时间16个月(1～30个月),2年总生存(OS)率(93.8±4.2)%,2年疾病无进展生存(PFS)率(84.4±6.3)%。初发组2年OS率为100%,2年PFS率为(94.7±5.0)%;复发、难治组2年OS率为(76.9±11.3)%,2年PFS率为(69.2±12.3)%,两组差异无统计学意义(P>0.05)。结论氟达拉滨为主的化疗方案患者耐受性较好,对低度恶性淋巴瘤疗效较好,有可能改善患者的预后。     

Salvage therapy for recurrent or refractory non-Hodgkin's lymphoma with etoposide, methotrexate, vindesine and prednisolone (EMVP)]

Seventeen patients with recurrent or refractory non-Hodgkin's lymphoma were treated with EMVP (Etoposide 75 mg/m2 i.v. d 1-5, Methotrexate 100mg/m2 i.v. d 1, Vindesine 3 mg/body i.v. d 1, Prednisolone 60 mg/m2 p.o. d 1-5), repeating every 3 weeks. Six complete responses (35%) and five partial responses (30%) were obtained with an overall response rate of 65%. The median duration of response was 26 months (range 8-49+months) for complete response (CR) and 4 months (range 2-6 months) for partial response (PR). The median duration of survival was 31 months for CR, 11 months for PR and 10 months for all patients, respectively. The major toxic effect was myelosuppression. Leukopenia less than 1,000/mm3 and thrombocytopenia less than 25,000/mm3 occurred in 5 and 3 patients, respectively. The other toxicities were alopecia, nausea and mucositis. However, these toxicities were well tolerated and clinically manageable. These results suggested that EMVP therapy was an effective regimen for patients with recurrent or refractory lymphoma.     

Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma

Background: High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and Methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin's disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III-IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.     

Salvage chemotherapy for non Hodgkin's lymphoma of unfavourable histology with a combination of CCNU and vinblastine

Twenty patients with relapsed or refractory, intermediate or high grade non Hodgkin's lymphoma were treated with a combination of CCNU and vinblastine. Complete responses occurred in four patients (20 per cent), partial responses in eight (40 per cent), for an overall response rate of 60 per cent. The regimen was more effective in patients with high grade lymphoma, absence of constitutional symptoms, better response to prior treatment. Duration of response was 4, 8, 16, 30 months for complete responders; 2, 2, 6, 6, 6, 8, 9, 14 months for partial responders. This combination regimen seems at least as effective as most of other regimens utilized in salvage treatment of non Hodgkin's lymphomas, with a very acceptable toxicity.     

Prolonged daily administration of oral etoposide in lymphoma following prior therapy with Adriamicin,an ifosfamide-containing salvage combination,and intravenous etoposide

Prolonged daily administration of oral etoposide has been reported to be active in refractory lymphoma. The purpose of this phase II trial was to confirm the activity of this schedule of etoposide in a selected group of heavily pretreated patients with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 26 patients (20 with NHL and 6 with HD) were entered in the trial; all had previously been treated with an Adriamycin-based chemotherapy, an ifosfamide-containing salvage combination, and i. v. etoposide. Etoposide was given in a fixed oral daily dose of 100 mg over 3 weeks; the weekly dose (500–700 mg) was selected such that the average daily dose was approximately 50 mg/m². Cycles were repeated on day 29. An objective response was seen in 16 patients (62%; 95% confidence interval, 42%–80%), with a complete response (CR) being observed in 3 cases (12%) and a partial response (PR), in 13 (50%). The median duration of PRs was 3 months. CRs lasted for 15 months in one patient and continue at 12+ and 20+ months in the remaining two patients. The overall actuarial survivial for the entire group was 40% at 2 years; the median survival time was 12 months. The main toxicity was myelosuppression; WHO grade 3 or 4 leukopenia and thrombocytopenia developed in 31% and 12% of the patients, respectively. There was no drug-related death. We conclude that oral etoposide is an effective and tolerable palliative treatment for heavily pretreated lymphoma patients.     

Immunochemotherapy with rituximab, vincristine and 5-day cyclophosphamide for heavily pretreated follicular lymphoma

PURPOSE: Therapeutic options for relapsed or refractory follicular lymphoma include combination chemotherapy, immunotherapy and, for selected patients, autotransplant. Because of the different mechanisms of action and non-overlapping toxicities, combination of rituximab with chemotherapy is a rational approach. METHODS: 30 patients with follicular non-Hodgkin's lymphoma with advanced-stage disease were treated with four cycles of immunochemotherapy with rituximab 375 mg/m2 on day 1, vincristine 2 mg i.v. on day 2 and cyclophosphamide 400 mg/m2 i.v. from days 2 to 6, repeated at 3-week intervals. All patients had received multiple lines of therapy (median 3); 9 (30%) had relapses (2 after high-dose therapy with autologous transplant), and 21 (70%) were in relapse and refractory to salvage treatment (with an anthracycline-containing regimen in 19). RESULTS: Of 29 patients evaluable for response, 16 (55 %) obtained a complete response (CR) and 3 (10%) a partial response (PR), with an overall response rate of 65% (19/29); 10 patients (35%) achieved less than PR. The median event-free survival was 16.1 months for all patients, being 22.8 months for responders. After a median follow-up of 2 years from the start of therapy (range 6 months to 3.8 years), of 16 patients who achieved CR, 10 remain free of disease. CONCLUSION: The combination of rituximab with vincristine and 5-day cyclophosphamide is able to produce CR in patients with advanced follicular lymphoma, even in patients resistant to third-generation regimens. The regimen designed on the basis of pharmacokinetics of the chimeric antibody seemed important for the clinical efficacy of the combination.     

Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease

Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers.     

Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP).

Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease.     

Short-term result of non-Hodgkin's lymphoma treated by the COMP regimen

From March 1982 to November 1984, 31 patients with non-Hodgkin's lymphoma were treated by COMP regimen. 15 (48%) had stage III and IV lesions. This regimen consisted of cyclophosphamide 600 mg IV weekly, vincristine 2 mg IV weekly, methotrexate 20 mg IM weekly and prednisone 30 mg PO daily for 2-3 weeks. Then, there was an interval of 2 weeks and the same therapy was repeated. 27 patients had more than 3 cycles. Of the 31 patients, 22 gave objective response with an overall response rate of 71%. Among the 22 patients without prior treatment, 10 (45.5%) achieved complete remission (CR) and 8 (36.3%) partial remission (PR)--the overall response rate was 81.8%. 4 (44%) of 9 patients with prior chemotherapy responded to COMP regimen (1 CR and 3 PR). The treatment was well-tolerated. There were only 9 patients with leukocyte count below 4000 and none of them ever below 2000. One patient had a transient elevation of serum glutamic pyruvic transaminase, which dropped to normal very quickly after interruption of the treatment. COMP regimen was as effective as COPP (procarbazine replacing methotrexate) regimen in non-Hodgkin's lymphoma. Hence, it could be considered as a common regimen for advanced non-Hodgkin's lymphoma and used to treat the patients refractory to certain chemotherapeutic agents.