Vincristine with high-dose etoposide in advanced breast cancer: a phase II trial of the Piedmont Oncology Association

Vincristine (VCR) and etoposide (VP-16) have been shown to be synergistic in a murine model, and this combination was studied in a phase II trial. Eligibility required measurable disease, a performance status of 0–2, a life expectancy of 2 months, an interval of at least 3 weeks since the receipt of previous radiation therapy or chemotherapy and recovery from related toxicity, no prior treatment with VCR or VP-16, and no more than two prior chemotherapy regimens (only one for treatment of metastatic disease). Treatment consisted of 0.5 mg i.v. (bolus) VCR followed by 200 mg/m² VP-16 given over 2 h. Both drugs were given daily for 3 consecutive days every 3 weeks (total dose: VCR, 1.5 mg; VP-16, 600 mg/m²). A total of 18 patients with metastatic breast cancer were accured; 14 had adjuvant chemotherapy and 8 had chemotherapy for advanced disease. As judged by International Union Against Cancer (UICC) criteria, one complete response (CR) and three partial responses (PR) were obtained, for a CR+PR rate of 22% (95% confidence interval, 6%–48%). All responders had soft-tissue involvement only. Six patients had stable disease and 8 showed progression. The median time to treatment failure was 3.5 months, and the median survival from study entry was 8.3 months. The major toxicity was myelosuppression, with 9 patients (50%) experiencing a total WBC of <1,000/mm³. Grade 2–3 neurologic toxicity was noted in 6 patients (33%) and grade 3 nausea and vomiting was noted in 5 (28%). The combination of VCR and VP-16 is active in advanced breast cancer but is not convincingly superior to either of these agents used alone.Supported in part by grants CA-12197, CA-37378, and CA-45808 from the National Institutes of Health, National Cancer Institute, Bethesda, Maryland     

VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.     

Cyclophosphamide,vincristine, cisplatin,VP-16 and radiation therapy in extensive small-cell lung cancer

Summary Patients with extensive small-cell lung cancer were given induction chemotherapy consisting of cyclophosphamide, vincristine, cisplatin, and etoposide (COPE) every 3 weeks for four cycles. Responding patients then received chest and elective whole-brain irradiation. Patients presenting with brain metastases received therapeutic brain irradiation during the first cycle of chemotherapy. No maintenance therapy was given, but two late intensification cycles of COPE were given at weeks 24 and 48. Among the 34 evaluable patients, the response rate to induction chemotherapy was 59%, with 10% achieving a complete response (CR) and 49%, a partial response (PR). Of the 18 patients who completed chest irradiation, 3 achieved a CR, producing an overall CR rate of 18%. Five patients completed the projected course of treatment. The median duration of response for all patients was 8 months (range, 2–30+ months) and the median survival was 9 months (range, 1–30+ months). Complete responders had a median response duration of 9 months and a median survival of 11 months. This regimen produced significant myelosuppression, with 5 neutropenic deaths (13%) occuring in the 38 patients evaluable for toxicity; an additional 16% required hospitalization for fever while neutropenic. Only six patients (13%) had nadir platelet counts of <50,000/mm³ with no episodes of thrombocytopenic hemorrhage. Nausea, vomiting, and neurotoxicity were mild to moderate in all patients. One patient with no evidence of disease died of radiation pneumonitis at 6 months. While producing significant toxicity, this regimen did not result in a CR rate or survival advantage that would suggest its superiority over standard regimens for small-cell lung cancer.This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA-20319, CA-37981, CA-13612, CA-22411, CA-12213, CA-32102     

A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Société Fran?aise d'Oncologie Pédiatrique

Forty-seven children or adolescents with initial stage IV (42 patients) or stage III (five) advanced neuroblastoma (12 were progressing after relapse and 35 had never reached complete remission [CR] after conventional therapy) were included in a phase II study of the combination of high-dose VP-16 (100 mg/m2/d X 5) and high-dose cisplatin (CDDP) (40 mg/m2/d X 5). Twenty patients had received prior CDDP therapy (total dose, 100 to 640 mg/m2; median, 320 mg/m2) and 38 of 47 had bone marrow involvement when included in the study. The overall response rate was 55%, with 22% CR. Duration of response was 5 to 18 months, with a median of 10 months. Eight patients are still disease free, with a median observation time of 13 months, but all had received additional therapy after two courses of this regimen. Gastrointestinal toxicity was frequent but tolerable. Myelosuppression was severe but of brief duration, ie, nadir of neutrophils was observed at day 15 with 95% of the patients recovering a normal count before day 28, and nadir of platelet count was at day 17 with only two severe and reversible episodes of bleeding. The overall incidence of sepsis was 8% (seven of 92 courses), with no death related to infection. No acute renal failure was observed after two courses, and only three of 47 children experienced a clear reduction of renal function. After two courses, only two children showed a hearing loss in the 1,000 to 2,000 Hz range, although hearing loss above the 2,000 Hz level was frequently encountered. It is concluded that high-dose VP-16 and CDDP is an effective regimen in advanced neuroblastoma with acceptable toxicity. Phase III studies are needed in previously untreated patients. J Clin Oncol 5:941-950.     

Cis-dichlorodiammineplatinum (Cis-platinum) and etoposide (VP-16) in malignant lymphoma — an effective salvage regimen

Summary Response rates in malignant lymphoma after failure of first-line therapy are generally poor. Twenty-five patients with non-Hodgkin's lymphoma (NHL) unresponsive to standard combination chemotherapy were treated with cis-platinum/VP-16. Alo were heavily pretreated, 29% having received three or more different drug regimens. Seventeen patients were evaluable for response. There were five complete remissions (CR) (29%) and four partial remissions (PR) (24%), giving an overall response rate of 53% (36% of all patients treated). The duration of CR was 12–48 weeks. Median survival for responders was 25 weeks (15–95), compared with only 5 weeks (4–17) for non-responders (P=0.002). Toxicity included nausea and vomiting, alopecia, minor renal impairment, and myelosuppression. This was sometimes severe: WBC<1.0x10⁹/l in three patients (18%) and platelets<50x10⁹/l in five patients (29%). The response rate for this combination is superior to that reported for either cisplatinum or VP-16 alone in similar patients (PR only 26% and 20%–30%, respectively). Further investigation is required to define the role of these drugs in the first-line treatment of poor-prognosis NHL.     

Treatment of patients with relapsed and resistant non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation.

PURPOSE: Patients with non-Hodgkin's lymphoma (NHL) who do not achieve a complete response (CR) after induction chemotherapy or who relapse after achieving a CR are rarely cured of their disease by the usual salvage therapy. Success of high-dose cytotoxic therapy with an autologous bone marrow transplant (AuBMT) is limited. We describe the results of a prospective single-institution study using a new conditioning regimen for patients with relapsed or resistant NHL who underwent AuBMT. PATIENTS AND METHODS: Forty-four patients were reinduced with cytotoxic therapy and then evaluated for response. All patients received the conditioning regimen of hyperfractionated total body irradiation (TBI), etoposide (VP-16), and cyclophosphamide (CTX) followed by autologous bone marrow reinfusion. RESULTS: The disease-free survival (DFS) rate was 57% with a median follow-up of 42+ months. The only variable significantly associated with DFS was the patient's remission status at AuBMT. Patients who underwent AuBMT in CR had a DFS of 80%, whereas patients who underwent AuBMT in partial response (PR) or with progressive disease (PD) had a DFS of 60% and 11%, respectively (P = .002). The major toxicity was hemorrhage at the site of bulky disease, especially in patients with residual mediastinal and/or pulmonary disease. CONCLUSION: Planned reinduction cytotoxic therapy followed by TBI, VP-16, and CTX with AuBMT is an effective treatment for patients with relapsed and resistant NHL.     

VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.     

Failure of IMVP-16 as second-line treatment for relapsed or refractory high grade non-Hodgkin's lymphoma.

The British National Lymphoma Investigation (BNLI) has assessed the use of an IMVP-16 regimen (ifosfamide, methotrexate, VP-16) in 46 patients with high grade non-Hodgkin's lymphoma (NHL) who on first-line chemotherapy either failed to attain a complete remission or relapsed. Seventeen patients responded to IMVP-16 but only five (11 per cent) went into a complete remission (CR), 12 (26 per cent) had a partial remission (PR) and 29 (63 per cent) showed no response (NR). CR after IMVP-16 has been maintained in only one case (36 months). The results of this study imply that the use of this IMVP-16 protocol as second-line treatment for patients with recurrent high grade NHL is unsuccessful and alternative salvage regimens should be sought.     

Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.     

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma

Purpose: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma.Patients and methods: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses.Results: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5–26). Eight CR patients remain in CR after 5–21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir <500/µl) and thrombocytopenia (platelet count nadir <50,000/µl) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2–4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/µl to 141/µl post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild.Conclusions: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.     

Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study.

A randomized study comparing teniposide (VM-26) and etoposide (VP-16) was performed to investigate whether there are any differences in the activity and toxicity of these two analogs in small-cell lung cancer (SCLC). Only previously untreated patients with SCLC were included; 46 and 48 patients receiving VP-16 and VM-26, respectively, are assessable for response. There were no differences between the two groups with respect to extent of disease, median age, and performance status (PS). The initial doses were for both compounds 70 mg/m2 intravenously (IV) daily for 5 days every 3 weeks. After inclusion of 25 patients in the study, the doses were increased to 80 mg/m2 for VM-26 and 90 mg/m2 for VP-16 because of differences in toxicity. VM-26 caused more hematologic toxicity than VP-16 throughout the study. The overall responses (complete response [CR] plus partial response [PR]) were 65% for VP-16 and 71% for VM-26, with CR occurring in 24% and 23%, respectively, for the two compounds. Median survival was 8.5 months for VP-16-treated patients versus 11.3 months for VM-26-treated patients (P = .58). It is concluded that both VP-16 and VM-26 are highly active single agents in SCLC.     

Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (Adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy

Seventy-one previously untreated patients with small cell lung cancer (SCLC) received a combination of VP-16, vincristine, doxorubicin (Adriamycin), and cyclophosphamide (EVAC) repeated every three weeks. Limited-disease (LD) patients and extensive-disease (ED) patients achieving a complete response (CR) or partial response (PR) after four to six cycles of EVAC received 4,000 rads over four weeks whole-brain radiotherapy (RT) and 5,000 rads over five weeks RT to the original pulmonary primary and mediastinum. ED patients with persisting disease outside the chest after six cycles of EVAC continued chemotherapy and did not receive RT. After RT was completed, EVAC was continued for a total treatment duration of 24 months. Of 65 patients evaluable for response 76% (25 of 33) of LD patients and 34% (11 of 32) of ED patients achieved a CR prior to RT; two additional ED patients achieved a CR after RT. Median survival for all 71 patients was 48 weeks (range, one to 207 weeks); median survival for 33 LD patients was 92 weeks and for 38 ED patients it was 36 weeks. Nine of 25 LD patients and 10 of 13 ED patients have relapsed from CR. The EVAC-RT protocol is promising in view of the high CR rate and long remission duration achieved, especially among patients with LD.     

DICE方案治疗复发或耐药中高度恶性非霍奇金淋巴瘤

背景与目的:复发或耐药非霍奇金淋巴瘤(non鄄Hodgkin蒺slymphoma,NHL)目前尚无标准的解救化疗方案,DICE、ESHAP、MINE和EPOCH等常见的解救治疗方案缓解率仅为30%～70%。本文旨在观察DICE方案作为解救化疗方案治疗复发或耐药中高度恶性NHL的疗效和安全性。方法:选取35例复发或耐药的中高度恶性NHL患者,其中T细胞和B细胞NHL分别为14和21例,既往接受过以CHOP或CHOP样方案为主中位6周期(2～12个周期)的化疗,采用DICE方案进行解救治疗。结果:35例患者接受了中位4周期(2～7个周期)的DICE方案化疗,所有患者均可评价疗效和不良反应。总的客观有效率为74.3%,完全缓解率为31.4%;中位缓解时间为4个月(1～30个月),中位至治疗失败时间为7个月(2～34个月),中位生存期为14个月(3～51个月),实际2年生存率为33.3%。T细胞和B细胞NHL的有效率分别为85.7%(12/14)和66.7%(14/21),完全缓解率分别为50.0%(7/14)和19.0%(4/21)(P=0.073)。LDH升高和伴有巨大肿块是影响解救治疗疗效的高危因素(P<0.05),DICE解救疗效是复发耐药患者生存期的独立预后因素(P=0.001)。主要不良反应为骨髓抑制,Ⅲ～Ⅳ度粒细胞和血小板减少的发生率分别为71.4%和8.6%。结论:DICE方案是复发或耐药中高度恶性NHL安全有效的解救治疗方案。LDH升高和伴有巨大     

放射治疗同时化疗Ⅲ期非小细胞肺癌

目的 评价放射治疗结合不同化疗方案治疗不能手术的Ⅲ期非小细胞肺癌（NSCLC）疗效。方法 62例不能手术的Ⅲ期NSCLC患者随机分为2个组：29例每周接受1次紫杉醇30mg、顺铂30mg化疗（紫杉醇组）,33例每周接受1次依托泊甙（VP-16）100mg、顺铂30mg化疗（VP-16组）。连续5～6周,均同时配合常规分割放射治疗（2Gy/次,5次/周）,照射野包括肺部原发灶和纵隔淋巴引流区,总剂量为60～70Gy。结果 紫杉醇组总有效（CR PR）为82.8%,完全缓解（CR）率为10.3%,VP-16组总有效率为54.6%,CR率为18.0%。2个组总有效率差异有显著性意义(X^2=4.41,P=0.038）。中位生存期、1、2年生存率紫杉醇组分别为12.8个月、52.2%、27.3%,VP-16组分别为9.8月、42.8%、18.4%,2个组差异无显著性意义。化疗的毒副作用主要是骨髓抑制和消化道反应,但均可耐受。结论 紫杉醇组治疗不能手术的Ⅲ期NSCLC近期有效率明显优于VP-16组,但不提高生存率。     

Alternating Non-Cross Resistant Chemotherapy for Small Cell Lung Cancer

After stratification for the extent of disease, previously untreatedpatients .with small cell lung cancer randomized to receivetherapy with the four-drug combination of cyclophosphamide,oncovin, nimustine hydrochloride (ACNU), and procarbazine (CONP)every four weeks (continuous regimen) or to receive CONP alternatingwith the three-drug combination of etoposide (VP-16), adriamycinand cisplatin (VAD) at four-week intervals (alternating regimen).Sixty-nine patients were entered in the study. Of 34 evaluablepatients receiving the continuous regimen, six (17.6%) achievedcomplete response (CR) and 16 (47.1%) achieved partial response(PR). Of 31 evaluable patients receiving the alternating regimen,10 (32.3%) achieved CR, and 16 (51.6%) achieved PR. There wasa tendency in favor of the alternating regimen in CR and overall response rates (0.05 < p < 0.1). There were no significantdifferences be tween the regimens in response duration or survival.The projected median survival times were 9.2 months and 9.4months for the continuous and alternating regimens, respectively.One patient receiving the continuous regimen and three receivingthe alternating regimen have been living for more than two years.The major toxicity was myelosuppression in both regimens. Onepatient died of hemorrhage due to thrombocytopenia during inductionwith CONP, and one patient died of cisplatin-induced renal failure.We conclude that alternating non-cross resistant chemotherapyleads to improved CR and response rates, but does not improvesurvival.     

Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma

BACKGROUND: In this international, multicenter trial, the authors evaluated rituximab (anti-CD20) plus epratuzumab (anti-CD22) in patients with postchemotherapy relapsed/refractory, indolent non-Hodgkin lymphoma (NHL), including long-term efficacy. METHODS: Forty-nine patients with follicular NHL (FL) (N = 41) or small lymphocytic lymphoma (SLL) (N = 7) received intravenous epratuzumab 360 mg/m2 and then intravenous rituximab 375 mg/m2 weekly x4. The regimen was tolerated well. RESULTS: Twenty-two of 41 patients with FL (54%) had an objective response (OR), including 10 (24%) complete responses (CR) (CR/unconfirmed CR [CRu]), whereas 4 of 7 patients with SLL (57%) had ORs, including 3 (43%) with CR/CRu. Rituximab-naive patients (N = 34) had an OR rate of 50% (26% CR/CRu rate), whereas patients who previously responded to rituximab (N = 14) had an OR rate of 64% (29% CR/CRu rate). An OR rate of 85% was observed in patients with FL who had Follicular Lymphoma International Prognostic Index (FLIPI) risk scores of 0 or 1 (N = 13), whereas 28 patients with intermediate or high-risk FLIPI scores (> or =2) had an OR rate of 39% (18% CR/CRu rate). In patients with FL, the median response duration was 13.4 months, and that duration increased to 29.1 months for 10 patients who had a CR/CRu, including 4 patients who had durable responses with remissions that continued for >4 years. In patients with SLL, the median response duration was 20 months, including 1 patient who had a response that continued for >3 years. CONCLUSIONS: The combination of epratuzumab and rituximab induced durable responses in patients with recurrent, indolent NHL.     

Intensive therapy for small-cell lung cancer using carboplatin alternating with cisplatin, ifosfamide, etoposide, mid-cycle vincristine, and radiotherapy.

Forty patients with small-cell lung cancer (31 patients with limited-stage [LS] disease, and nine patients with extensive-stage [ES] disease but of good performance status) have been treated with an intensive therapy composed of carboplatin alternating with cisplatin, ifosfamide, and etoposide with vincristine on day 14 of each carboplatin cycle. A maximum of six cycles were administered at 3 weekly intervals after the cisplatin combination and 4 weekly after the carboplatin combination. Prophylactic cranial irradiation was given with the first cycle of chemotherapy and thoracic irradiation with the third cycle. The median nadir for neutrophils was 0.47 x 10(9)/L and for platelets, 40 x 10(9)/L. Chemotherapy dosages were not reduced in response to myelosuppression, but treatment was delayed to allow blood count recovery. Sixty-eight percent of patients received all six cycles of chemotherapy, and there were four deaths associated with treatment-related neutropenia. Twenty-eight patients (70%) achieved a complete response (CR) when assessed 1 month after the end of treatment, and a further five patients (12.5%) had a partial response (PR). Median duration of CR was 16 months and of PR, 8 months. Cerebral metastases occurred in 20% of all patients and was the apparent sole site of relapse in 11% of the CR patients. The median survival of the total group was 14 months with an actual 2-year survival of 30% and a minimum follow-up of 28 months.     

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL)

Summary In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m² with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median folow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial test MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.for the Yorkshire Lymphoma Group (YLG)     

Etoposide (VP-16) in the treatment of advanced adenocarcinoma of the pancreas

Twenty-six patients with advanced adenocarcinoma of the pancreas were treated with etoposide (VP-16), 100-180 mg/m2 i.v., days 1, 2, and 3, monthly. Twenty-five had bidimensionally measurable disease and one had evaluable disease only. This regimen and dosage schedule were well tolerated, with minimal toxicity including myelosuppression; a median WBC count nadir of 3,600 cells/mm3 (range 200-2,400); and a median platelet nadir of 215,000 cells/mm3 (range 15,000-405,000). However, no patients responded and only two had stable disease for 3.5 and 4 months, respectively. At this dosage and schedule, there is no role for VP-16 in the treatment of advanced pancreatic adenocarcinoma.     

Fractionated cyclophosphamide, vincristine, liposomal daunorubicin (daunoXome), and dexamethasone (hyperCVXD) regimen in Richter's syndrome.

Approximately 3 to 5% of patients with chronic lymphocytic leukemia (CLL) develop an aggressive large cell non Hodgkin's lymphoma (NHL) known as Richter's syndrome (RS). RS has a poor prognosis and a response rate of < 10% with fludarabine-based or other cytotoxic combination regimens. The aim of this study was to evaluate the efficacy and toxicity of the hyperCVXD regimen in RS. Twenty-nine patients, median age 61 years (36-75) 23 males, were treated. Prior diagnosis was CLL in 26 patients, NHL in 2, and Prolymphocytic leukemia in 1. Treatment consisted of fractionated cyclophosphamide, vincristine, daunoXome and dexamethasone. Six patients (20%) died while receiving study therapy, 4 (14%) during the first cycle of whom 2 had started therapy with overt pneumonia. Grade 4 granulocytopenia occurred in all 95 cycles of therapy with a median time to recovery of 14 days. Twenty three (24%) cycles were complicated by fever, and 15 (15%) by pneumonia. Sepsis was documented in 8 (8%) cycles, and neuropathy in 5 (5%) of cycles. Twenty three patients had a platelet count < 100 x 10(9)/l prior to therapy: a greater than 50% decrease in platelet count over pre-therapy level occurred in 79% of first cycles, overt bleeding occurred in 4 (4%) of all cycles. Eleven of 29 (38%) patients achieved complete remission (CR), 4 of whom have relapsed after 5, 6, 9, and 12 months of remission. Two of 11 CR patients presented with RS without any prior CLL therapy. One patient had a partial remission. Thus the overall response rate was 12/29 (41%). Overall median survival was 10 months, 19 months in patients who achieved CR, 3 months in those who did not (p = 0.0008). A landmark analysis performed at 2 months from start of therapy comparing patients alive in CR versus patients alive but not in CR showed a median survival of 19 months versus 6 months, respectively (p 0.0017). In conclusion the hyper CVXD regimen has a relatively high response rate, significant toxicity and a moderate impact on survival in RS.