Phase II Randomized Trial of Temozolomide and Concurrent Radiotherapy in Patients With Brain Metastases

2002 ◽  
Vol 20 (17) ◽  
pp. 3644-3650 ◽  
Author(s):  
D. Antonadou ◽  
M. Paraskevaidis ◽  
G. Sarris ◽  
N. Coliarakis ◽  
I. Economou ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Randomized Trial ◽  
Response Rate ◽  
External Beam Radiotherapy ◽  
Objective Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Neurologic Symptom ◽  
Symptom Evaluation ◽  
Radiotherapy Alone

PURPOSE: To determine the efficacy, tolerability, and safety of concurrent temozolomide and radiotherapy in patients with previously untreated brain metastases. PATIENTS AND METHODS: Fifty-two patients with brain metastases from solid tumors were randomized to oral temozolomide (75 mg/m2/d) concurrent with 40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4 weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and radiotherapy continued temozolomide therapy (200 mg/m2/d) for 5 days every 28 days for an additional six cycles. The primary end points were radiologic response and neurologic symptom evaluation. RESULTS: The objective response rate was significantly (P = .017) improved in patients receiving temozolomide and radiotherapy versus radiotherapy alone. Among 24 patients assessable for response in the temozolomide group, 23 (96%) of 24 responded, including nine (38%) patients with a complete response and 14 (58%) patients with a partial response. With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including seven (33%) complete responses and seven (33%) partial responses. There was marked neurologic improvement in the group receiving temozolomide, and the proportion of patients requiring corticosteroids 2 months after treatment was lower in the temozolomide group compared with radiotherapy alone (67% v 91%, respectively). Daily temozolomide concurrent with radiotherapy was generally well tolerated; however, grade ≥ 2 nausea (48% v 13%, P = .13) and vomiting (32% v 0%, P = .004) were significantly increased in the temozolomide group. Hematologic toxicity was predictable and reversible. CONCLUSION: Temozolomide is safe, and a significant improvement in response rate was observed when administered in combination with radiotherapy in patients with previously untreated brain metastases. A larger randomized trial is warranted to verify these results.

Vincristine, irinotecan, and temozolomide in patients with relapsed and refractory neuroblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22009-e22009
Author(s):  
Jia Zhu ◽  
Zijun Zhen ◽  
Juan Wang ◽  
Tingting Chen ◽  
Suying Lu ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Salvage Regimen ◽  
Brain Involvement ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Grade Iii

e22009 Background: The combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed or refractory neuroblastoma (NB). Methods: Forty-six patients with relapsed or refractory NB were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2 /day i.v. days 1–5) and temozolomide (100 mg/m2 /day p.o. days 1–5) (VIT) during the period 2011–2019. All toxicities were documented. Results: A total of 251 cycles (median 6 cycles/patient) were administered. A complete response (CR) was achieved in 5 patients, partial response (PR) in 27 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 6 patients, with an overall objective response rate (CR+PR) of 69.6%. Eighteen patients developed diarrhea with Grade III or less. Grade 1-2 hematologic toxicity occurred in 10 patients. Grade 3-4 hematologic toxicity developed in 32 patients. VIT was an effective regimen for different metastatic sites. Overall objective response rates to VIT combination for patients with mediastinum, bone marrow/bone, lymph node, abdomen and brain involvement were 100.0%, 80.0%, 77.8%, 50.0%, 42.9%, respectively. UGT1A*28 genotyping performed in 7 patients revealed wild type. Diarrhea occurred in 4 of them. Conclusions: The shorter, 5-day VIT regimen is an active and well-tolerated salvage regimen in relapse/refractory NB.[Table: see text]

scholarly journals Effects of S-1 combined with radiotherapy in the treatment of nasopharyngeal cancer: a meta-analysis based on randomized controlled trials

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 107-114
Author(s):  
Jin Fengtong ◽  
Fu Jiangtao ◽  
Wang Yating ◽  
Wu Lili ◽  
Chen Jianbo ◽  
...  
Keyword(s):  
Survival Rate ◽  
Partial Response ◽  
Objective Response Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Objective Response ◽  
Complete Response ◽  
Effect Model ◽  
Radiotherapy Alone

AbstractThe aim of this meta-analysis was to evaluate the effects and toxicity of S-1 combined with radiotherapy in the treatment of nasopharyngeal cancer (NPC). Through a search of the databases of PubMed, Embase, the Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang system and Chongqing VIP Information (CQVIP), the efficacy and side effects data of S-1 combined with radiotherapy in the treatment of NPC patients from open published randomized controlled trials (RCTs) were collected. The pooled complete response (CR), partial response (PR), objective response rate (ORR), 2-year survival rate and treatment related toxicity were analyzed by Stata12.0 software. Eight RCTs with 599 cases were included and analyzed in this meta-analysis. The general quality of the 8 studies were deemed as having moderate risk of bias. Adequate sequence generation was reported in 4 studies. Incomplete outcome data address was reported in 7 publications. Five studies indicated to be free of selective reporting. Seven studies reported the treatment complete response (CR) between S-1 combined with radiotherapy and radiotherapy alone. With significant heterogeneity, the data was pooled by random effect model. The pooled results indicated that S-1 combined with radiotherapy can significant increase the CR rate compared to radiotherapy alone (RR=1.52, 95%CI:1.33-1.74, P<0.05). Eight studies reported the partial response (PR) rate between the combined treatment and radiotherapy alone. The pooled results showed that there was no statistical difference for PR between combined treatment and radiotherapy alone (RR=0.85, 95%CI:0.62-1.16, P>0.05). For the effect size of objective response rate (ORR), pooled results indicated that S-1 combined with radiotherapy can significantly increased the ORR by random effect model (RR=1.39, 95%CI:1.23-1.57, P<0.05). The pooled results showed that S-1 combined with radiotherapy significant increase the risk of developing bone marrow suppression (RR=1.94, 95%CI:1.40-2.69, P<0.05) and gastrointestinal reaction (RR=1.81, 95%CI:1.38-2.38, P<0.05) with fixed effect model. However, the pooled oral mucositis (RR=1.22, 95%CI:0.99-1.50, P>0.05) and radiodermatitis (RR=0.93, 95%CI:0.77-1.12, P<0.05) were not statistically different. Two studies reported the 2-year survival rate between the two groups. The pooled results showed the combined treatment significantly increased the 2-year survival rate for patients with nasopharyngeal carcinoma (RR=1.14, 95%CI:1.01-1.28, P<0.05). The funnel plot demonstrated significant publication bias for complete response, partial response, objective response rate and oral mucositis. The egger’s line regression test indicated significant publication bias for complete response (t=5.98, P=0.002) and objective response rate(t=6.23, P=0.003). Conclusion S-1 combined with radiotherapy can significant improve the clinical efficacy with more treatment related toxicity compared to radiotherapy alone in the treatment of nasopharyngeal carcinoma.

scholarly journals Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4091-4101
Author(s):  
Arne Kolstad ◽  
Tim Illidge ◽  
Nils Bolstad ◽  
Signe Spetalen ◽  
Ulf Madsbu ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

scholarly journals Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy

Blood ◽  
1981 ◽  
Vol 58 (5) ◽  
pp. 920-925 ◽  
Author(s):  
JH Glick ◽  
JM Barnes ◽  
EZ Ezdinli ◽  
CW Berard ◽  
EL Orlow ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Response Duration ◽  
Complete Response ◽  
Drug Regimen ◽  
Late Relapse ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Disease Free

Abstract Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3–4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

1998 ◽  
Vol 16 (4) ◽  
pp. 1388-1396 ◽  
Author(s):  
J P Sculier ◽  
M Paesmans ◽  
J Thiriaux ◽  
J Lecomte ◽  
G Bureau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Randomized Trial ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Moderate Dose

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

scholarly journals Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097535 ◽  
Author(s):  
Stefano Kim ◽  
Aurélia Meurisse ◽  
Laurie Spehner ◽  
Morgane Stouvenot ◽  
Eric François ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Pooled Analysis ◽  
Term Survival ◽  
Anal Squamous Cell Carcinoma

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies. Patients & methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen. Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, ( p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 ( p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( n = 54) and mDCF ( n = 58) in terms of OS ( p = 0.57) and PFS ( p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed. Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced-stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study.

1991 ◽  
Vol 9 (10) ◽  
pp. 1793-1800 ◽  
Author(s):  
J Grem ◽  
P O'Dwyer ◽  
P Elson ◽  
N Simon ◽  
D Trump ◽  
...  
Keyword(s):  
Clinical Response ◽  
Response Rate ◽  
Residual Disease ◽  
Eastern Cooperative Oncology Group ◽  
Dose Intensity ◽  
Complete Response ◽  
Clinical Response Rate ◽  
Hematologic Toxicity ◽  
Survival Times ◽  
Moderate Nausea

Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification.

Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.

1997 ◽  
Vol 15 (2) ◽  
pp. 458-465 ◽  
Author(s):  
J M Sorensen ◽  
D A Vena ◽  
A Fallavollita ◽  
H G Chun ◽  
B D Cheson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
National Cancer Institute ◽  
Response Rate ◽  
Performance Status ◽  
Treatment Protocol ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Motor Dysfunction ◽  
Hematologic Toxicity ◽  
Contributing Factors

PURPOSE To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

Phase II Results of Bendamustine in Combination with Rituximab in Relapsed Indolent and Mantle-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2710-2710 ◽  
Author(s):  
Richard H. Van der Jagt ◽  
Philip Cohen ◽  
Bruce D. Cheson ◽  
Anil Tulpule ◽  
Jordan A. Herst ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Prior Chemotherapy ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

Abstract Objective: The objective of this study was to evaluate the efficacy and safety of bendamustine HCl (TREANDA®) in combination with rituximab in patients with relapsed non-Hodgkin’s lymphoma (NHL). Background: Bendamustine is a novel hybrid, alkylating agent with single-agent activity in multiple hematologic and solid tumors. It induces cell death via both apoptosis and the apoptosis-independent pathway of mitotic catastrophe. The combination of bendamustine and rituximab has been shown to exhibit a synergistic antitumor effect on NHL cells. Methods: This Phase II, multicenter study enrolled adult patients with relapsed, indolent B-cell or mantle-cell NHL who were not refractory to rituximab (defined as progression ≤6 months of last rituximab dose). Patients received rituximab 375 mg/m2 intravenously (IV) on day 1 and bendamustine 90 mg/m2 IV on days 2 and 3 of a 28-day cycle for 4 to 6 cycles. An additional dose of rituximab 375 mg/m2 IV was given 1 week before the first cycle of bendamustine and 4 weeks after the last cycle. Results: The intent-to-treat (ITT) population included 66 patients (59% men) with a median age of 60 years (range, 40–84). Indolent histologic phenotype was seen in 54 patients with the following histologic subtypes: follicular center cell (61%), small lymphocytic (15%), lymphoplasmacytic (3%), and marginal zone (3%); 18% had mantle-cell lymphoma (MCL). A total of 85% of patients had stage III/IV disease. These patients relapsed from a median of 1 prior chemotherapy (range: 0–5), with 56% having had prior treatment with rituximab. Patients with no prior chemotherapy relapsed following biologic therapy. In the ITT population, the overall objective response rate (ORR) was 94% (complete response [CR]/complete response unconfirmed [CRu], 41%; partial response [PR], 53%); 6% had stable disease. The ORR for the 12 MCL patients was 92% (CR/CRu, 42%; PR 50%). For all patients, the median duration of response and progression-free survival has not been reached after a median follow-up of 8.3 months (range, 0.14–31 months). Grade 3/4 neutropenia was seen in 41% of patients (7%, febrile neutropenia). Common nonhematologic toxicities (grade 1/2, grade 3, grade 4) were nausea (68%, 0%, 0%) and fatigue (53%, 5%, 0%); one patient had grade 3 sepsis. No alopecia was observed. Conclusions: Bendamustine administered in combination with rituximab produced a high objective response rate and was generally well tolerated in patients with relapsed indolent and mantle-cell NHL who were not refractory to rituximab. These results suggest that the combination of bendamustine and rituximab may be comparable in activity to R-CHOP, and further studies of this combination are warranted.

Comparison of Results from a Phase 1/2 Study of Lumiliximab (Anti-CD23) in Combination with FCR for Patients with Relapsed CLL with Published FCR Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 32-32 ◽  
Author(s):  
John C. Byrd ◽  
Januario Castro ◽  
Susan O’Brien ◽  
Ian W. Flinn ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Response Rate ◽  
Phase 1 ◽  
Performance Status ◽  
Randomized Study ◽  
Complete Response ◽  
Cancer Center ◽  
Published Data ◽  
Hematologic Toxicity ◽  
Variable Regions ◽  
Overall Response

Abstract Lumiliximab is a PRIMATIZED® anti-CD23 monoclonal antibody with human IgG1 constant regions and macaque variable regions. Preclinical data demonstrated that lumiliximab enhanced both fludarabine- and rituximab- mediated apoptosis in CLL cells. Thus, a Phase 1/2, open-label, dose-escalation, multicenter study (Study 152–30) evaluating lumiliximab + fludarabine, cyclophosphamide, and rituximab (L + FCR) for relapsed CD23+ B-cell CLL was initiated. Treatment has been completed and follow-up is ongoing. Thirty-one patients (pts) received either 375 mg/m2 (n=3) or 500 mg/m2 (n=28) of lumiliximab in combination with a 28-day cycle of FCR for up to 6 cycles. Median age at study entry was 58 yrs. The majority of pts (74%) were Rai Stage I/II. The most common adverse events included nausea (77%), pyrexia (61%), chills (55%), neutropenia (55%), and fatigue (48%). Twenty pts (65%) experienced a Grade 3 or 4 event. An overall response rate of 71% was demonstrated: 48% complete response (CR), 10% partial response (PR), and 13% unconfirmed PR. Currently, baseline cytogenetic data is available for 21 pts who received 500 mg/m2 of lumiliximab. Although preliminary, 1 of the 4 pts with del(17p13.1) responded; of the 6 pts with del(11q22.3), 5 responded with 4 attaining a CR. A comparison with published data from a study of FCR alone in 177 pts with relapsed or refractory CLL conducted at the M.D. Anderson Cancer Center (MDACC) (Wierda W, O’Brien S, Wen S, et al. J Clin Oncol.2005;23:4070–4078) demonstrated that L + FCR has an acceptable safety profile, does not appear to increase the toxicity (including myelosuppression) of the FCR regimen, and compares favorably with the CR rate of the FCR regimen alone, as displayed in Table 1. Most pt characteristics (age, gender, median number of prior therapies, and WHO performance status) were similar between the 2 studies; however, more pts in the MDACC study were Rai Stage III-IV (50% vs 22%) and were rituximab-naïve (88% vs 40%). Furthermore, there were no obvious differences in hematologic toxicity between the 2 studies and the tolerability of L + FCR was similar to that of FCR, with approximately 50% percent of pts completing 6 cycles of treatment in both studies. These data suggest that L + FCR may produce a higher complete response rate than FCR without additional toxicity. Based upon this data, a multicenter, global, randomized study of L + FCR vs. FCR alone is being initiated. Table 1. Comparison of Responses in Study 152–30 and the MDACC Study Study 152–30, L + FCR (N=31), n (%) MDACC, FCR (N =177), n (%) 1CR and PR response criteria were the same in both studies. 2PRu is included in the OR. Overall Response 22 (71%) 130 (73%) Complete Response1 15 (48%) 45 (25%) Partial Response1 3 (10%) 85 (48%) Unconfirmed Partial Response2 4 (13%)

Sign in / Sign up

Export Citation Format

Share Document