MINE方案治疗复发或耐药的侵袭性淋巴瘤临床观察

背景与目的:复发或耐药侵袭性非霍奇金淋巴瘤(non-HodgkinQslymphoma,NHL)的治疗是当前恶性淋巴瘤治疗的难题,目前尚无标准的挽救性治疗方案。本研究目的是观察MINE方案(Mesna、IFO、Novantrone、VP-16)治疗复发或耐药侵袭性NHL的疗效和不良反应。方法:回顾性分析2001年1月至2003年6月收治的38例复发或耐药侵袭性NHL患者的临床资料,所有患者均接受过至少1个化疗方案的治疗,中位方案数为2个(1～4个),中位疗程数6个(2～12个)。采用MINE方案化疗2～6个疗程(中位疗程数4个)。结果:38例患者均可评价疗效和不良反应,总有效率47.4%,完全缓解率15.8%。B细胞来源淋巴瘤(26例)有效率57.7%,T细胞来源淋巴瘤(12例)有效率25.0%。全组1年生存率34.2%,2年生存率7.9%。主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度白细胞减少发生率为39.5%(15例),Ⅲ～Ⅳ度血小板减少发生率为13.2%(5例);1例患者出现Ⅲ度肝功能损害。结论:MINE方案为复发或耐药侵袭性NHL的经济、有效挽救治疗方案,不良反应可以耐受,但缓解时间较短,值得进一步研究应用。     

Docetaxel monotherapy in heavily pretreated metastatic breast cancer: a multicenter, community-based feasibility trial

PURPOSE: To evaluate the efficacy and safety of docetaxel in heavily pretreated and anthracycline-resistant patients with metastatic breast cancer in an outpatient setting. PATIENTS AND METHODS: Between February 1996 and June 1998, 98 consecutive patients who had progressed during or relapsed following prior anthracycline-containing chemotherapy were enrolled into the trial. Docetaxel was administered at a dose of 100 mg/m2 by intravenous infusion every 3 weeks. The administration of colony-stimulating factors was at the discretion of the attending physician. Premedication with dexamethasone was mandatory for all patients. RESULTS: Of the 98 patients, 93 were evaluable for toxicity and response. Patients had received two palliative regimens (median, range 1-5) prior to docetaxel treatment. The most frequent toxicity observed was leukopenia grade III and IV (WHO grading system) which occurred in 47% of patients (grade IV only in 14%). Except for alopecia grade III (64% of patients), nonhematologic side effects grade III-IV were rare (1-7% of patients) and included nausea, stomatitis, diarrhea, peripheral neuropathy, fluid retention and pulmonary toxicities. There were no treatment-related deaths. Objective responses occurred in 40% of patients (CR 6%, PR 34%), and stable disease in 38% of patients. The median duration of response was 5.3 months (range 0.7-18.1 months) while the median survival was 15 months (range 2 36 months). CONCLUSION: Docetaxel is a highly active agent in patients with anthracycline-resistant metastatic breast cancer, even in heavily pretreated patients, with moderate toxicity.     

Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.     

异环磷酰胺联合化疗治疗恶性肿瘤临床观察

［目的］评价异环磷酰胺联合化疗治疗多种晚期恶性肿瘤的疗效及毒性。［方法］１９９５年１０月～１９９８年４月,５５例晚期非小细胞肺癌、恶性淋巴瘤和乳腺癌等肿瘤患者接受合异环磷酰胺为主的联合化疗,其中非小细胞肺癌２８例,恶性淋巴瘤８例,乳腺癌７例,其他肿瘤１２例。肺癌的化疗方案为ＭＩＣ和ＮＩＰ方案,恶性淋巴瘤为ＩＨＯＰ和ＭＩＶＥ方案,乳腺癌为ＩＡＦ和ＩＭＦ方案。［结果］５５例患者可评价疗效和毒性。总有效率５０．９％,ＣＲ８例,ＰＲ２０例。肺癌、恶性淋巴瘤和乳腺癌有效率分别为 ３９．３％,７５．０％和５７．１％。白细胞减少率为８９．１％,３～４级减少分别为３６．４％。血红蛋白减少和血小板减少分别为６９．１％和３８．２％,３级以上减少少见。非血液学毒性主要有恶心、呕吐４９．１％,脱发６５．５％,肝功能异常１６．４％。［结论］异环磷酸胺联合化疗作为一、二线治疗对多种晚期恶性肿瘤均有一定疗效。含异环磷酰胺的化疗方案及提高异环磷酰胺剂量强度治疗常见恶性肿瘤,值得临床深入研究。     

DICE方案治疗复发或耐药侵袭性淋巴瘤的临床研究

 目的　观察DICE方案治疗复发或耐药侵袭性非霍奇金淋巴瘤（NHL）的疗效和患者的不良反应。方法　50 例复发或耐药侵袭性NHL患者均接受过至少1 种化疗方案的治疗,中位方案数为2（1～4）种,中位疗程数6（2～12）个 。DICE 方案：异环磷酰胺（IFO）1.5 g／m2加入生理盐水100 ml静脉滴注,第1天至第3天;巯乙磺酸钠（商品名：美斯钠）400 mg 加入生理盐水30 ml,分别于IFO 的同时及之后4 h 和8 h 静脉注射,第1天至第3天;顺铂（DDP） 20 mg／m2静脉滴注,第1天至第4天;依托泊苷（ VP16） 50 mg／m2口服,第1天至第5天。地塞米松（DEX）20 mg／m2第1天至第7天,每3 周为1 个疗程。化疗2～6 个疗程（中位疗程数4 个）。结果　50 例患者均可评价疗效和不良反应,总有效率46.0 %（23例）,完全缓解率16.0 %（8例）。B 细胞来源淋巴瘤（26例）有效率53.84 %,T细胞来源淋巴瘤（24例）有效率29.2 %。全组1 年生存率34.0 %,2年生存率8.0 %。主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度白细胞减少发生率为38.0 %（19例）,Ⅲ～Ⅳ度血小板减少发生率为14.0 %（7例）;1例患者出现Ⅲ度肝功能损害。结论　DICE方案为复发或耐药侵袭性NHL患者经济、有效的挽救治疗方案,不良反应可以耐受,但缓解时间较短,值得进一步研究应用。     

VAPEC-B chemotherapy in the treatment of aggressive non-Hodgkin's lymphoma: A retrospective analysis of 45 patients

We performed a retrospective analysis on 45 patients who, between January 1989 and October 1993, received VAPEC-B chemotherapy for high and intermediate grade non-Hodgkin's lymphoma. The aim was to assess response and tolerance to treatment. The weekly regimen consisted of: doxorubicin 35 mg/m² i.v. weeks 1,3,5,7,9,11; cyclophosphamide 350 mg/m² i.v. weeks 1, 5, 9; etoposide 100 mg/m² p.o. daily for 5 days, weeks 3,7,11; vincristine 1.4 mg/m² i.v. (2 mg max.) weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m² i.v. weeks 2, 6, 10; methotrexate 12.5 mg i.t. weeks 1, 5, 9; prednisolone 50 mg p.o. daily for 6 weeks, reduced to 25 mg daily for 6 weeks. The patients treated were aged 22–71 years, 34 (75%) had high grade (Working Formulation) non-Hodgkin's lymphoma (NHL); 11 (24%) had intermediate grade NHL; 25 had Stage III/IV disease; and 14 (31%) had marrow involvement. The majority of patients (76%) received VAPEC-B as first line chemotherapy; the remainder received it for relapsing disease. Follow-up time from completion of VAPEC-B chemotherapy ranged from 6 months to 50 months (median 25). VAPEC-B, as first line therapy, induced a complete response (CR) and partial response (PR) in 79% and 18% respectively, whilst 3% had no response to treatment. VAPEC-B used for relapsing disease produced CR and PR in 64% and 27% respectively, whilst 9% failed to respond. Six patients in PR and five patients in CR have subsequently undergone an autologous bone marrow transplant or a peripheral blood stem cell transplant. In the group who received VAPEC-B first line but did not proceed to transplant (27 patients), five relapsed (three with CNS disease who had not had CNS prophylaxis). Tolerance to treatment was measured by WHO toxicity scores. The haemoglobin (Hb) toxicity median score for all patients was grade 1 (Hb 9.5–10.9 g/dl), and the white cell count (WCC), toxicity score was grade 2 (WCC 2.0–2.9 × 10⁹/l). No platelet toxicity was observed. Ten per cent of patients suffered grade 3 severity infections requiring antibiotics and there was one treatment related death. The majority of patients received VAPEC-B on time, however, 24% patients had a 2-week delay.VAPEC-B chemotherapy is an effective regimen for malignant lymphoma, either as a first line or as a salvage treatment. Although chemotherapy was given weekly, the tolerance to treatment was acceptable, thus making this short regimen a good alternative to CHOP chemotherapy.     

Salvage extended-field irradiation in follicular non-Hodgkin's lymphoma after failure of chemotherapy

PURPOSE: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1983 to 1998, 34 patients received TAI (n = 22) or TBI (n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1-5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. RESULTS: Mean follow-up from TAI or TBI was 120 months (range, 6-180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. CONCLUSION: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.     

Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma

The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.     

Ifosfamide plus mitoxantrone as salvage treatment in non-Hodgkin's lymphomas

Twenty-two patients affected by relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with a combination of ifosfamide (IFO) at the dose of 1.2 g/m2 intravenous (i.v.) (1 h infusion) for 5 consecutive days with mesna as uroprotector plus mitoxantrone (NOV) at the dose of 12 mg/m2 i.v. on day 1; both drugs were recycled every 3-4 weeks. Of 21 evaluable patients, overall response observed was 57% (38% complete response and 19% partial response with a median duration of response of 7 months (5-23+). Dose-limiting toxicity was represented by leukopenia (grade III-IV in 43% of cases); severe thrombocytopenia was observed less frequently (grade III-IV in 19% of cases). This hematologic toxicity prevented administration of therapy every 3 weeks as initially planned. However, the complete hematological recovery, usually observed at the fourth week, permitted therapy administration to all patients without dose reduction. Low-grade lymphomas responded to treatment as well as intermediate or high grade lymphomas. Moreover, patients treated with third- or fourth-line chemotherapy also responded. However, response was observed in 11/13 (85%) relapsed patients as compared to 2/8 (25%) refractory cases. The combination of IFO plus NOV is active in heavily pretreated patients with NHL. Nevertheless, the study of a larger number of patients is necessary to better define the exact role of this combination as "salvage" therapy for NHL.     

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.     

Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma

Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for survival and recurrence-free survival (RFS) was malignancy grade. Probability of uncorrected survival at 10 years for low, intermediate, and high grade was resp. 34, 0 and 0%. Probability of RFS at 10 years was resp. 19, 0, and 0%. Neither stage nor sex had any influence on survival. Age was reversely correlated with survival, but was not correlated with RFS. Influence of prior therapy (18 patients) on survival and RFS was separately analyzed. Neither survival nor RFS of unfavorable histologic type NHL (high and intermediate grade) was influenced. On the other hand patients with a favorable histologic type NHL (low grade) had a significantly (p less than 0.05) better RFS if they received LTBI as initial treatment, but survival was not significantly influenced. RFS at 5 and 10 years of patients who received LTBI as first treatment was respectively 32% and 27%. No treatment related complications were noted. Subsequent chemotherapy in case of relapse was not hampered by previous LTBI. The high response rate and extended RFS, without maintenance therapy, makes LTBI a preferable first line treatment for patients with advanced stage low grade NHL.     

Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the minnie pearl cancer research network.

PURPOSE: To evaluate the feasibility and efficacy of rituximab with short-duration chemotherapy in the first-line treatment of patients with follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with previously untreated stage II-IV follicular NHL, grade 1 or 2, were eligible for this multicenter phase II trial. All patients received four weekly doses of rituximab (375 mg/m(2) intravenous), followed by three courses of combination chemotherapy (either cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], or cyclophosphamide, vincristine, and prednisone [CVP]) plus rituximab. Patients were evaluated for response after completing treatment, and were then followed up at 3-month intervals. RESULTS: Between January 2000 and July 2001, 86 patients were treated. Eight-two patients (95%) completed treatment; no patient was withdrawn due to toxicity. The overall response rate was 93%, with 55% complete responses. After a median follow-up of 42 months, the 3- and 4-year actuarial progression-free survivals were 71% and 62%, respectively. Five patients (6%) died from lymphoma; the overall actuarial survival at 3 years was 95%. Grade 3/4 leukopenia occurred in 53% of patients, but only six patients (7%) had neutropenia or fever. Grade 3/4 nonhematologic toxicities were uncommon. CONCLUSION: Rituximab plus short-course chemotherapy is well tolerated as first-line treatment for patients with follicular NHL. The overall and complete response rates are similar to those reported with chemotherapy/rituximab combinations of longer duration. The actuarial progression-free survival of 62% at 4 years is encouraging, but further follow-up is necessary. Rituximab plus short-course chemotherapy may prove to be as effective as longer-duration chemotherapy and currently provides an attractive option for first-line treatment of elderly patients and others who tolerate chemotherapy poorly.     

Activity of thalidomide in patients with platinum-refractory germ-cell tumours

The aim of this study was assess the activity of thalidomide in patients with progressive relapsed or platinum-refractory germ-cell tumours (GCT). Between April 2002 and January 2003, 15 patients with inoperable progressive GCT were treated with escalated daily doses of 200-600 mg thalidomide. All patients had failed first-line and salvage chemotherapy with a median of 6 (range 4-12) cisplatin-based treatment cycles, 13/15 (87%) patients had received high-dose chemotherapy (HDCT) and 8/15 (53%) patients were considered platinum-refractory or absolute refractory; 8/15 (53%) patients had previously received other palliative chemotherapy regimens. No patient achieved a complete remission (CR) or partial remission (PR). However, 5/15 (33%) patients achieved serological PR and 1 additional patient had stable disease for 3 months. The median duration of remissions was 3 months (range 2-12 months) including 2 patients with a progression-free survival of 9 and 12 months. Responses occurred mainly in patients with a low tumour burden, slow disease progression and alpha-foetoprotein (AFP) elevations. Responses to thalidomide were independent from platinum-sensitivity. Toxicity was mild, with lethargy and constipation in the majority of patients. Skin rash grade II developed in 2 patients and peripheral neurotoxicity grade II/III developed in 4 patients. One responding patient died suddenly from an unknown cause. It is concluded that thalidomide shows single-agent activity in patients with heavily pre-treated GCT, AFP elevations and slowly progressive disease.     

High dose chemotherapy without hematopoietic cell support for the treatment of refractory lymphoma

Conventional dose combination chemotherapy for patients with relapsed or refractory lymphoma is rarely curative. High dose chemotherapy followed by hematopoietic progenitor cell transplant (HPCT) has a clearly defined role in patients who have first relapsed after standard CHOP chemotherapy for lymphoma. However, the role of HPCT is less well defined for patients with chemo-resistant, or chemo-refractory disease. Sixteen patients (15 Non-Hodgkin's, 1 Hodgkin's Disease) were entered into a phase II study to determine if a dose intensive induction regimen in heavily pre-treated refractory lymphoma patients could permit further consolidation with HPCT. The primary endpoints were survival, response, toxicity, and resource utilization. The regimen consisted of continuous infusion etoposide 1 or 2 gm/m2/72 hours, idarubicin 12 mg/m2/d for 3 days followed by cytarabine 2 gm/m2/72 hours on days 8, 9, and 10 (VIC). Fifteen patients were evaluable for objective response. The overall response rate was 53% with 7 patients achieving a partial response and 1 patient achieving a complete response. Of the 8 responders, 6 patients subsequently received high dose chemotherapy followed by HPCT (4 autologous, 2 allogeneic). The median survival was 176 days for the non-responders contrasted with 722 days for the responders. The average duration of hospitalization was 38 days. Toxicity was mainfest primarily as mucositis with a median grade of 3 among the first 13 patients, and a median grade of 2 in three subsequent patients who received an etoposide dose of 1 gm/m2/72 hours. All patients had an episode of neutropenic fever and 5 patients developed clinically significant pneumonitis during therapy. The VIC regimen is active in the treatment of chemo-refractory lymphoma with clinically significant differences in survival for patients who respond to therapy. Further modifications to the regimen could include the addition of a topoisomerase I inhibitor for synergy with etoposide, and using VIC as part of a tandem transplant regimen where response to VIC would allow further therapy with a myeloablative induction followed by HPCT.     

Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma.

PURPOSE: To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL). PATIENTS AND METHODS: Patients with indolent and MCL were eligible. Bortezomib was given at a dose of 1.5 mg/m2 on days 1, 4, 8, and 11. Patients were required to have received no more than three prior chemotherapy regimens, with at least 1 month since the prior treatment, 3 months from prior rituximab, and 7 days from prior corticosteroids; absolute neutrophil count more than 1,500/microL (500/microL if documented bone marrow involvement); and platelet count more than 50,000/microL. RESULTS: Twenty-six patients were registered, of whom 24 were assessable. Ten patients had follicular lymphoma, 11 had MCL, three had small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), and two had marginal zone lymphoma. The overall response rate was 58%, with one complete remission (CR), one unconfirmed CR (CRu), and four partial remissions (PR) among patients with follicular non-Hodgkin's lymphoma (NHL). All responses were durable, lasting from 3 to 24+ months. One patient with MCL achieved a CRu, four achieved a PR, and four had stable disease. One patient with MCL maintained his remission for 19 months. Both patients with marginal zone lymphoma achieved PR lasting 8+ and 11+ months, respectively. Patients with SLL or CLL have yet to respond. Overall, the drug was well tolerated, with only one grade 4 toxicity (hyponatremia). The most common grade 3 toxicities were lymphopenia (n = 14) and thrombocytopenia (n = 7). CONCLUSION: These data suggest that bortezomib was well tolerated and has significant single-agent activity in patients with certain subtypes of NHL.     

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.     

2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies.

2''-Chlorodeoxyadenosine (2CDA) is a purine analogue selectively active against both resting and dividing lymphoid cells. Twenty-one patients with a variety of previously treated lymphoid malignancies received a total of 41 courses of 2CDA (0.1-0.15 mg/kg/day over 7 days continuous intravenous infusion) on compassionate grounds. The profile of the patient population was as follows: low grade non-Hodgkin''s lymphoma (NHL) = 8, intermediate grade NHL = 2, transformed (intermediate grade NHL) = 6, Hodgkin''s disease = 1, lymphoplasmacytoid NHL = 3 and lymphoblastic NHL = 1. The overall response rate was 53%, with three patients attaining complete remission (CR) and eight partial remission (PR). Three of 16 patients with primary resistant or resistant recurrent disease entered either CR (1) or PR (2). Ten patients had no response or progressive disease. The latter group was comprised of patients who had extensively pre-treated lymphoplasmacytoid tumours and/or poor performance status (WHO grades 2-4). The median duration of response is 6 months (range 1 to 12 months). Treatment was well tolerated and the chief toxicities were leucopenia and thrombocytopenia which were most pronounced when there was bone marrow involvement. As a result of dose limiting myelotoxicity, a dose escalation to 0.15 mg/kg/day was possible on just three occasions. These data confirm other reports of the activity of 2CDA in low grade NHL and indicate it may have activity in Hodgkin''s disease. There was no demonstrable activity in poor performance status patients or those with extensively pre-treated lymphoplasmacytoid tumours.     

Clinical features of testicular non-Hodgkin's lymphoma--focus on treatment strategy

Testicular primary non-Hodgkin's lymphoma (NHL) is said to account for about 5% of all testicular tumors and about 2% of extranodular lymphoma. From a clinical standpoint, we reviewed testicular NHL of stage IE treated at our department over the past 18 years. Among the 865 cases of NHL, 19 (2.2%) were primary testicular NHL, stage IE. The 19 patients had a median age of 62 years (range 48-77 years), all had diffuse B-cell lymphoma. Of the 19 patients, 8 were treated with radiotherapy after high inguinal orchiectomy (Group I), 4 received both postoperative radiotherapy and chemotherapy (Group II), and 7 received additional prophylactic intrathecal chemotherapy (Group III). The 5-year survival rates for Groups I, II and III were 37.5%, 50%, and 100%, respectively. None of the patients receiving prophylactic intrathecal chemotherapy had relapse in the central nervous system and all of them are alive and disease-free. Primary testicular NHL is relatively common among elderly persons, and many patients die as a result of central nervous system recurrence. These results suggest that preventive measures for central nervous system recurrence such as intrathecal injection of anticancer agents should be taken into consideration as early as at the induction of remission.     

Clinical Features of Testicular Non-Hodgkin's Lymphoma: Focus on Treatment Strategy

Testicular primary non-Hodgkin's lymphoma (NHL) is said to account for about 5% of all testicular tumors and about 2% of extranodular lymphoma. From a clinical standpoint, we reviewed testicular NHL of stage IE treated at our department over the past 18 years. Among the 865 cases of NHL, 19 (2.2%) were primary testicular NHL, stage IE. The 19 patients had a median age of 62 years (range 48-77 years), all had diffuse B-cell lymphoma. Of the 19 patients, 8 were treated with radiotherapy after high inguinal orchiectomy (Group I), 4 received both postoperative radiotherapy and chemotherapy (Group II), and 7 received additional prophylactic intrathecal chemotherapy (Group III). The 5-year survival rates for Groups I, II and III were 37.5%, 50%, and 100%, respectively. None of the patients receiving prophylactic intrathecal chemotherapy had relapse in the central nervous system and all of them are alive and disease-free. Primary testicular NHL is relatively common among elderly persons, and many patients die as a result of central nervous system recurrence. These results suggest that preventive measures for central nervous system recurrence such as intrathecal injection of anticancer agents should be taken into consideration as early as at the induction of remission.     

Phase II trail of didemnin B in previously treated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group (ECOG) Study

Patients with non-Hodgkin's lymphoma (NHL) who fail initial therapy have a poor prognosis. We conducted a phase II study to determine the efficacy and toxicity of didemnin B, a non-myelosuppressive marine compound, in patients with NHL who relapsed or progressed after receiving one or two previous chemotherapy regimens. Fifty-one eligible patients were registered on this phase II study. Twenty-nine patients had intermediate or high grade (IG/HG) disease and 22 patients had low grade (LG) disease. Twenty-five patients received didemnin B at a dose of 6.3 mg/m2 and the remainder received 5.6 mg/m2, administered intravenously every 28 days. The patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and biopsy-proven relapsed disease. Objective responses were observed in two (7%) patients (one complete remission [CR] and one partial remission [PR]) with IG/HG disease and five (23%) patients (one CR and four PR) with LG disease. Patients with IG/HG disease had a median time to treatment failure (TTF) of 1.6 months and a median survival of 8.0 months. In contrast, the group with LG disease had a median TTF of 4.6 months and a median survival of 2.7 years. There were five grade V, 12 grade IV, and 57 grade III toxicities. Didemnin B appears to have modest activity in low grade NHL. However, the drug has considerable toxicity in this population of patients.