Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma

BACKGROUND: Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma (NHL). METHODS: Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles in the absence of disease progression. RESULTS: Thirty-one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum-containing therapy. Eighty-three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13-47%) of the patients. Responses were observed in platinum-naive patients as well as in those previously treated with platinum. The overall median failure-free survival duration was 3.0 months (range, 0.1-18.1 months). CONCLUSIONS: Oxaliplatin had favorable single-agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL.     

Low-dose weekly paclitaxel for recurrent or refractory aggressive non-Hodgkin lymphoma

BACKGROUND: Many patients with recurrent, intermediate or high-grade non-Hodgkin lymphoma (NHL) may not respond to or are not candidates for aggressive salvage chemotherapy. Effective, less toxic regimens are needed. Although high-dose taxanes have not been reported to be very effective for the treatment of lymphoma, different delivery rates may allow for different mechanisms of action to be manifest and result in a different toxicity profile and response rate. The current study tested this hypothesis by using low-dose, weekly paclitaxel in patients with recurrent or refractory NHL. METHODS: Adults age > 18 years with refractory or recurrent, aggressive NHL who were not considered curable with standard high-dose therapy received paclitaxel at a dose of 80 mg/m2 weekly for 5 weeks for 2 cycles. RESULTS: Thirty-four patients with refractory NHL and 4 patients with recurrent disease were treated. Approximately 45% of the patients had achieved a prior disease remission. The median number of prior regimens received was 3, 74% of the patients had an International Prognostic Index of > or = 3 at the time of study entry, and 29% had failed high-dose therapy with autologous hematopoietic support. Only one patient encountered severe toxicity (sepsis). Myelosuppression was reported to occur in approximately 20% of patients. A total of 10 patients (26%) achieved a complete disease response and 4 patients (11%) achieved a partial response. CONCLUSIONS: In the current study, low-dose, weekly paclitaxel therapy was found to provide a well tolerated and less toxic approach to the treatment of refractory NHL, with encouraging responses noted in heavily pretreated patients. However, evaluation in patients with an earlier stage of disease is warranted.     

Phase 2 study of fludarabine and paclitaxel in patients with recurrent low-grade non-Hodgkin's lymphoma

Although numerous options are available for patients with recurrent low-grade non-Hodgkin's lymphoma (NHL), responses are rarely durable. We previously conducted a phase I trial of fludarabine and paclitaxel in the treatment of recurrent low-grade lymphoma. The present phase II study was performed to determine the activity of fludarabine and paclitaxel in patients with recurrent low-grade NHL. Patients with histologically confirmed recurrent low-grade NHL were treated with fludarabine 20 mg/m2/day intravenously (i.v.) on days 1-5 plus paclitaxel 50 mg/m2 given by i.v. continuous infusion over 72 h starting on day 1. Treatment was repeated at 4-week intervals for a maximum of six courses. Twenty-eight evaluable patients were entered into this phase II trial. The median age was 53 years and the median performance status (Zubrod) was 1. Twenty-two (78%) patients had grade 1 or 2 follicular lymphoma, and six patients (21%) had small lymphocytic lymphoma. The median number of prior chemotherapy regimens was 1 (range, 1-3). Objective responses occurred in 16 patients (57%); nine patients (32%) achieved a complete remission with a median duration of 32 months (range 4-84+ months), and seven patients (25%) had a partial remission. Grade 3 and 4 toxicities included neutropenia (72%), neutropenic fever (34%), infection (13%), mucositis (7%), and neuropathy (3%). The combination of fludarabine and paclitaxel has clinical activity in patients with recurrent low-grade NHL.     

Multicenter Phase II study of estramustine phosphate plus weekly paclitaxel in patients with androgen-independent prostate carcinoma

BACKGROUND: The current study determined the efficacy and toxicity of weekly paclitaxel in combination with estramustine phosphate (EMP) in patients with androgen-independent prostate carcinoma (AIPC). METHODS: Patients with progressive AIPC received 90 mg/m2 paclitaxel by 1-hour intravenous infusion weekly for 3 weeks, followed by a 1-week treatment rest. Patients received 140 mg EMP orally 3 times daily on the day before, the day of, and the day after paclitaxel administration. Patients received 1 mg warfarin daily to prevent thromboembolism. RESULTS: Sixty-six patients with progressive AIPC received treatment at 29 centers. Forty-two percent of patients had a 50% decline in prostate-specific antigen (PSA; 95% confidence interval [CI], 30-54%). For 26 patients with bidimensionally measurable disease, the objective response rate was 15% (95% CI, 1-30%). The median time to disease progression was 6.3 months, and the median time to PSA progression was 11.4 months. The median survival period was 15.6 months. Grade 3-4 toxicities were uncommon and included thromboembolism (8%), anemia (3%), neutropenia (3%), and peripheral neuropathy (2%). There was one treatment-related death. CONCLUSIONS: This regimen of EMP plus weekly paclitaxel was an active and well tolerated treatment for patients with AIPC.     

Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan

Tazemetostat is a selective, reversible, small-molecule inhibitor of the histone methyltransferase enzyme, enhancer of zest homolog 2 (EZH2). In this multicenter, open-label, phase II study, we assessed the efficacy and safety of tazemetostat in Japanese patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma harboring the EZH2 mutation. Tazemetostat (800 mg twice daily) was given orally (28-day cycle) until disease progression or unacceptable toxicity. Among the 20 eligible patients, 17 were enrolled in cohort 1 (follicular lymphoma [FL]), and three were enrolled in cohort 2 (diffuse large B-cell lymphoma). At data cut-off, the objective response rate in cohort 1 was 76.5%, including six patients (35.3%) with complete response and seven patients (41.2%) with partial response (PR). All three patients in cohort 2 achieved PR. In cohort 1, median progression-free survival (PFS) was not reached at the median follow-up of 12.9 months. The estimated PFS rate at 12 and 15 months was 94.1% and 73.2%, respectively. The most common grade 3 treatment-emergent adverse event (TEAE) was lymphopenia (n = 2). Grade 4 TEAEs included hypertriglyceridemia and pneumonia aspiration (n = 1 each), which were not related to tazemetostat. Treatment-emergent adverse events leading to study drug discontinuation were reported in four of the 20 patients, indicating that the safety profile of tazemetostat was acceptable and manageable. Tazemetostat 800 mg twice daily showed encouraging efficacy in patients with R/R EZH2 mutation-positive FL with a manageable safety profile in the overall population. Thus, tazemetostat could be a potential treatment for R/R EZH2 mutation-positive FL.     

Phase 2 study of irinotecan and paclitaxel in patients with recurrent or refractory small cell lung cancer

BACKGROUND:

Patients with extensive stage small cell lung cancer (SCLC) who develop disease progression with standard cisplatin‐based therapy are reported to have a poor overall prognosis. Irinotecan and paclitaxel are active as single agents and exhibit preclinical synergy in SCLC cell lines. A phase 2 study was conducted to evaluate this combination in patients with recurrent or refractory SCLC.

METHODS:

Patients with SCLC who progressed with 1 prior chemotherapy regimen and had measurable disease present; an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2; and adequate bone marrow, hepatic, and renal function were included in the study. Paclitaxel (at a dose of 75 mg/m²) and irinotecan (at a dose of 50 mg/m²) were administered intravenously on Days 1 and 8 of each 3‐week treatment cycle. Therapy was continued until disease progression or unacceptable toxicity. The target response rate of interest was ≥30%.

RESULTS:

A total of 55 patients were enrolled, 51 of whom received at least 1 dose of therapy. The majority of the patients had an ECOG PS of 0 or 1 (96%). A median of 3 cycles of treatment was administered, and 15 patients received ≥6 cycles. Seventeen patients experienced toxicity of grade 3 or higher (neutropenia in 8 patients and fatigue in 5 patients). The overall response rate was 21%. The median survival was 25.4 weeks, and the 1‐year survival rate was 22%.

CONCLUSIONS:

The regimen of irinotecan and paclitaxel was found to be tolerated well in patients with recurrent or refractory SCLC. Although modest anticancer activity was noted, the efficacy failed to meet the primary endpoint of interest. Cancer 2010. © 2010 American Cancer Society.     

Phase II study of docetaxel in patients with relapsed or refractory malignant lymphoma

We report the activity and toxicity of docetaxel in 12 evaluable heavily pretreated patients with relapsed and refractory non-Hodgkin's lymphoma and Hodgkin's disease. In all, 42% achieved a partial response, 25% achieved stable disease. Median duration of response was 16 (10-21) weeks. The median overall survival was 70 (9-178) weeks and for responders it was 120 (22-178) weeks. One patient developed one episode of neutropenic sepsis. Docetaxel has limited activity in this group of patients.     

Phase II study of paclitaxel in patients with metastatic breast carcinoma refractory to standard chemotherapy

BACKGROUND: The authors conducted a single institution Phase II clinical trial to determine whether paclitaxel had antitumor activity in patients with metastatic breast carcinoma that was refractory to standard chemotherapy. METHODS: Patients with metastatic breast carcinoma were eligible for the study if they had disease progression after at least 2 prior chemotherapy regimens. Patients who had received three prior regimens were treated in a separate cohort. All patients were required to have received doxorubicin in the past and were not eligible if they had received prior therapy with paclitaxel. The starting dose of paclitaxel for low risk patients was 175 mg/m2, administered as a 24-hour continuous infusion; the starting dose of paclitaxel was 150 mg/m2 for patients who had received > or = 3 prior regimens. Therapy was given every 3 weeks and continued for at least 2 courses unless there was evidence of rapidly progressing disease, for at least 3 courses if there was no change in disease and Grade 3 or 4 (based on National Cancer Institute toxicity criteria) toxicity was not noted, and for 6 courses beyond the maximum response in patients who demonstrated complete or partial responses and showed no evidence of disease progression. RESULTS: Sixty-eight of 69 patients entered in the study were evaluable for response: 35 patients who had received 2 prior chemotherapy regimens for Stage IV disease and 33 patients who had received > or =3 prior regimens. A partial response was observed in 7 patients who had received 2 prior regimens, for an objective response rate of 20% (95% confidence interval [95% CI], 14-26%). In the group who had received > or = 3 prior regimens, a total of 6 partial responses were observed, for an objective response rate of 18% (95% CI, 12-23%). The median response duration was 8.2 months (range, 2.7-10.1 months) for the group who had received 2 prior regimens and 5.8 months (range, 2.1-9.5 months) for patients who received > or = 3 prior regimens. Responses were noted in patients with anthracycline-resistant tumors. CONCLUSIONS: Paclitaxel was active in heavily pretreated patients with metastatic breast carcinoma, including anthracycline-resistant breast carcinoma.     

Phase II study of PEND chemotherapy in patients with refractory/relapsed Hodgkin lymphoma

High-dose chemotherapy with autologous marrow or stem cell rescue (HDC/ASCT) is an effective strategy in patients with relapsed Hodgkin lymphoma. Various chemotherapy regimens have been used for cytoreduction prior to HDC/ASCT. In this study, our objective was to determine the response rate to PEND in a group of patients with relapsed Hodgkin lymphoma. Nineteen patients with relapsed or primary refractory Hodgkin lymphoma underwent treatment with the PEND regimen and received a median of 2 cycles (1 - 6 cycles). The PEND regimen builds on our prior results with ABDIC and consists of prednisone 40 mg/m² orally (PO) daily × 5 days; etoposide 50 mg/m² PO daily × 14 days; mitoxantrone 5 mg/m²/d IV, days 1 and 3; and DTIC 200 mg/m²/d intravenous continuous infusion (CIV) over 24 h, days 1 to 5, via central venous catheter. The treatment was given every 28 days. There were 3 complete responses (16%) and 10 partial responses (53%) yielding a total response rate of 69% (95% C.I. 43%, 87%). Myelosuppression was the predominant toxicity; no deaths were due to toxicity. After achieving maximum response to PEND, 10 eligible patients received a consolidative treatment with HDC/ASCT. All 6 patients who did not respond to PEND died from disease progression whereas 5 of 13 responders were alive after 10 years of follow-up (3 without disease). There were 11 deaths due to disease progression; three from other causes. The initial response to PEND before subsequent ASCT consolidation treatment appears to be associated with survival. All patients who failed to achieve a response have died. We conclude that PEND is an effective treatment strategy in Hodgkin lymphoma patients previously treated with both ABVD and MOPP.     

Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma

BACKGROUND: The management of recurrent or refractory Hodgkin lymphoma (HL) remains challenging. The objective of this phase 2 trial was to investigate the activity of gemcitabine in combination with rituximab in patients with recurring or refractory HL. METHODS: Patients were considered eligible if they had recurring or refractory HL, had received >or=2 prior chemotherapy regimens, had an Eastern Cooperative Oncology Group (ECOG) performance status 相似文献   

A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma

Purpose: Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and topotecan have separately demonstrated activity against gliomas. We conducted a Phase II trial of these agents in combination with filgrastim (G-CSF) in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.Patients and Methods: Adult patients with radiographic evidence of recurrent or progressive tumor following primary therapy were eligible for study. Patients received paclitaxel 175 mg/m² IV over 3 h on day 1 and topotecan 1.0 mg/m ² IV over 30 min on days 1–5. Filgrastim 5 g/kg was given days 6–14 for neutrophil support. Treatment cycles were repeated every 21 days.Results: Twenty patients were enrolled on study, and seventeen were considered evaluable for response. Two patients (12/%) exhibited partial remission and seven patients (41/%) exhibited stable disease in response to therapy. Hematologic toxicity was common with 25 /% of patients experiencing grade III or IV leukopenia despite G-CSF support. Two patients died of infectious complications on protocol, prompting suspension of further accrual.Conclusion: Paclitaxel and topotecan with G-CSF support exhibits modest activity in adults with recurrent or refractory glioblastoma and anaplastic astrocytoma. The significant hematotoxicity encountered, however, cannot justify further investigation of this combination in patients with high grade brain tumors.Supported with grant funding from: GlaxoSmithKline Pharmaceuticals Collegeville, PA     

Phase II study of sphingosomal vincristine in patients with recurrent or refractory adult acute lymphocytic leukemia

BACKGROUND: Outcomes with salvage therapy for patients with recurrent or refractory acute lymphocytic leukemia (ALL) are poor, with complete response (CR) rates reported to be 20-30% and a median survival ranging from 2-6 months. New agents are needed to reduce the recurrence rate after frontline chemotherapy. Vincristine is an important component of ALL therapy. In animal models, the encapsulation of vincristine into sphingomyelin liposomes or "sphingosomes" for injection (SV) has improved efficacy compared with conventional vincristine. METHODS: A Phase II clinical trial of single-agent SV given at a dose of 2.0 mg/m2 every 2 weeks was conducted in patients with recurrent or refractory ALL. Approximately half of the 16 patients who received SV had a first CR duration of less than 1 year, 19% had failed standard induction chemotherapy, and 50% had Philadelphia chromosome-positive disease. SV was the first salvage attempt in 69% of the patients. RESULTS: The overall response rate in the 14 evaluable patients was 14% (1 CR and 1 partial response). Five patients (36%) had transient reductions in bone marrow leukemia infiltrate with subsequent regrowth of the leukemia between SV infusions. Toxicity with limited treatment (median number of doses was two; range, one to five doses) was minimal with expected peripheral neuropathy. CONCLUSIONS: Further study of SV in patients with ALL is warranted. A Phase I-II clinical trial of weekly SV with pulse dexamethasone currently is ongoing.     

Phase II evaluation of oral estramustine, oral etoposide, and intravenous paclitaxel in patients with hormone-sensitive prostate adenocarcinoma

Purpose

The primary objective of this study was to assess the feasibility and efficacy of administering etoposide/estramustine/paclitaxel in hormone-sensitive metastatic prostate cancer responding to hormonal therapy.

Patients and Methods

Eligible patients had metastatic prostate cancer and had received combined androgen blockade for 6-8 months with a ≤ 80% decrease in prostate-specific antigen from pretreatment. They received 4 cycles of chemotherapy consisting of estramustine 280 mg orally 3 times daily, etoposide 50 mg/m² orally on days 1-14, and paclitaxel 135 mg/m² intravenously for 1 hour on day 2 of each 21-day cycle and were then followed until time to treatment failure (TTF).

Results

Twenty-six patients were evaluable for response and toxicity. Median TTF was 21.7 months (range, 11.9-64.5 months; 95% confidence interval, 15.3-26.2 months). Median survival from time of initiation of hormone therapy was 5.1 years. Neutropenia was the most common grade 3/4 toxicity, occurring in 3 patients. Significant toxicities were limited to nausea, diarrhea, and febrile neutropenia in 3 patients, respectively.

Conclusion

The administration of paclitaxel/estramustine/etoposide in this setting is feasible and well tolerated. Although the TTF of 21.7 months by prostate-specific antigen criteria is similar to historical controls in the emergence of clinically evident androgen-independent disease after starting hormone therapy, direct comparisons cannot be made. More trials are needed to investigate the timing of chemotherapy in patients with prostate cancer.     

A Phase II study of paclitaxel and ifosfamide for patients with advanced refractory carcinoma of the urothelium.

BACKGROUND: Cisplatin-based combination chemotherapy for patients with advanced transitional cell carcinoma (TCC) of the urothelium has limitations, and new therapies need to be evaluated. METHODS: Ifosfamide 1.0 gm/m2 on Days 1-4 and paclitaxel 135 mg/m2 by 24-hour infusion on Day 4 were administered to 26 patients with locally unresectable or metastatic TCC. Cycles were repeated every 21 days for a maximum of 6 cycles; dose escalation was dependent on whether Grade 3 or 4 toxicities occurred. RESULTS: There were 24 males and 2 females, with a median age of 66 years and a median Eastern Cooperative Oncology Group performance status of 0. The median number of cycles administered was 3. Twelve patients had Grade 3 or 4 hematologic toxicities, including 1 patient who died of a gastrointestinal hemorrhage while pancytopenic. There were no episodes of neutropenic fever. Two patients each had a complete response (CR) that lasted 5 and 28 months, respectively (response rate: 15%; 95% CI: 2-45%), among the 13 patients who had received prior chemotherapy. Of the 13 patients without prior chemotherapy, there were 3 with complete responses and 1 with a partial response ranging from 8 to 25+ months (RR: 30.7%; 95% CI: 9-61%). CONCLUSIONS: The combination of ifosfamide and paclitaxel is well tolerated and can produce objective responses in patients who are chemona?ve or have had prior therapy. For previously untreated patients, the addition of ifosfamide does not appear to result in a better response rate than single agent paclitaxel; and for previously treated patients, the addition of paclitaxel does not appear to result in a better response rate than single agent ifosfamide.     

A Phase I/II study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma

BACKGROUND: The maximum tolerated dose (MTD) and efficacy of weekly 1-hour paclitaxel with 3 days of high dose oral estramustine were evaluated in patients with hormone-refractory prostate carcinoma. METHODS: Patients enrolled in cohorts of three received two cycles of six weekly treatments with 1 week of rest: Cohort I received paclitaxel 40 mg/m2 and estramustine 600 mg/m2, and Cohorts II-IV received paclitaxel 60 mg/m2, 75 mg/m2, or 90 mg/m2, respectively, and estramustine 900 mg/m2. Toxicity was assessed weekly, and response was measured by serum prostate specific antigen (PSA), abdominal computed tomography scans, and bone scans at Week 13. RESULTS: Eighteen patients were enrolled, with 12 in Cohorts III and IV. Four patients did not complete treatment. Grade 3 toxicity included one patient with nausea and diarrhea in Cohort III and one patient each with neutropenia and edema followed by Grade 4 thromboembolism in Cohort IV. Grade 1-2 anemia or myelotoxicity were not observed; 3 patients had neuropathy, 5 patients had hair loss, and 8 patients had gastrointestinal symptoms. A decline in the serum PSA level > or = 50% occurred in none of three patients, one of three patients, four of six patients, and four of six patients in Cohorts I-IV, respectively. An intent-to-treat analysis showed responses in 9 of 18 patients (50%) in Cohorts I-IV, with 9 of 15 responders (60%) in Cohorts II-IV. Seven patients achieved declines in serum PSA levels > 75%. The median duration of PSA response was 16.7 weeks. Response was observed in one of three patients with measurable disease. CONCLUSIONS: The MTD for 1-hour weekly paclitaxel was 90 mg/m2 with 3 days of 900 mg/m2 estramustine. Hematologic and neurotoxicity were reduced markedly, and gastrointestinal symptoms were ameliorated, but thromboembolic events were unaffected. PSA response rates were within the expected 60% range for these agents.     

Phase II study of weekly low-dose paclitaxel for relapsed and refractory non-Hodgkin's lymphoma: a Wisconsin Oncology Network Study

This study was performed to determine the clinical activity and safety of weekly low-dose paclitaxel (90 mg/m2) given as a 1-hour infusion in patients with relapsed and refractory non-Hodgkin's lymphoma (NHL). Thirty patients were treated on a phase II protocol conducted at the University of Wisconsin Comprehensive Cancer Center and within the Wisconsin Oncology Network (WON). A cycle of therapy was defined as paclitaxel at 90 mg/m2 weekly for 6 consecutive weeks followed by a 2-week rest period. Cycles were repeated as long as there was no disease progression or unacceptable toxicity. In general, the patients were heavily pretreated with a median of 4 prior therapies (range 2-11), and 73% were refractory to the most recent systemic therapy. The median age was 70 (range 44-97). All NHL histological subtypes were eligible. Of the 30 eligible patients enrolled, 26 were evaluable for response and 28 for toxicity. The overall response rate was 23% (95% confidence interval (CI) 9.0-43.7%). One patient had a complete response, and 5 patients had partial responses. The median response duration was 3.2 months (range 1.4-11.8 months). The median event-free survival was 1.9 months. The major toxicity was neuropathy. Despite the limited marrow reserve in this patient population, myelosuppression was minimal. Paclitaxel given in this dose and schedule has modest activity in previously treated non-Hodgkin's lymphoma. The response rate appears similar to other reports using different doses and schedules. Myelosuppression appears less with this schedule than with other schedules.     

Phase II study of amonafide in patients with recurrent glioma

Summary Amonafide, a novel imide derivative with broad preclinical antitumor activity, achieves significant cerebrospinal fluid levels in animal models. In order to test its antitumor activity in patients with recurrent diffuse infiltrative glioma of the astrocytic and oligodendroglial type, we performed a phase II clinical trial. Of the 22 eligible and evaluable patients treated, 2 (9%) experienced tumor regression lasting more than one year. No other patients experienced tumor regression; one remained stable more than six months. Toxicities consisted primarily of myelosuppression, vomiting, and venous irritation at the infusion site. We conclude that amonafide has minimal activity in recurrent glioma patients. Further investigations are not warranted in this study population.     

GDP方案治疗复发难治性非霍奇金淋巴瘤的临床观察

,尤其血小板下降,Ⅲ～Ⅳ度血小板下降占全组29.63%.无治疗相关死亡.结论:GDP方案是治疗复发难治性非霍奇金淋巴瘤的一个有效方案,毒副反应可以耐受.     

Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma

E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin-2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We undertook a multicenter, single-arm phase II study of E7777 in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) to evaluate its efficacy, safety, pharmacokinetics, and immunogenicity. A total of 37 patients were enrolled, of which 17 and 19 patients had PTCL and CTCL, respectively, and one patient with another type of lymphoma (extranodal natural killer/T-cell lymphoma, nasal type), diagnosed by the Central Pathological Diagnosis Committee. Among the 36 patients with PTCL and CTCL, objective response rate based on the independent review was 36% (41% and 31%, respectively). The median progression-free survival was 3.1 months (2.1 months in PTCL and 4.2 months in CTCL). The common adverse events (AEs) observed were increased aspartate aminotransferase (AST) / alanine aminotransferase (ALT), hypoalbuminemia, lymphopenia, and pyrexia. Our results indicated that a 9 µg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common AEs were manageable, but increase in ALT / AST, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment.