Bendamustine Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle Cell Lymphoma (MCL): Final Results of a Japanese Multicenter Phase II Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3694-3694 ◽  
Author(s):  
Michinori Ogura ◽  
Toshiki Uchida ◽  
Kiyoshi Ando ◽  
Ken Ohmachi ◽  
Kuniaki Itoh ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Multicenter Phase ◽  
Number Of Patients ◽  
Highly Effective ◽  
Grade 3

Abstract Abstract 3694 Poster Board III-630 [Background and Purpose] Bendamustine hydrochloride is a bifunctional alkylating agent with novel mechanisms of action. Although bendamustine is known to have anti-tumor activity against indolent B-NHL as a single agent, efficacy in MCL with bendamustine monotherapy has not been reported. To assess the efficacy and toxicity of bendamustine in patients with relapsed indolent B-NHL and MCL, we conducted a multicenter phase II study. [Patients and Methods] Patients diagnosed with relapsed or refractory indolent B-NHL or MCL, 75= or >age= or >20, and PS 0-1 (ECOG) were enrolled in the study. Bendamustine was administered intravenously at a dose of 120 mg/m2 infused over 60 minutes on days 1 and 2 of each 21-day treatment cycle for up to 6 cycles (minimum of 3 cycles). The primary endpoint was the overall response rate (ORR). Tumor response was assessed by a central radiological review committee according to the International Workshop Criteria for NHL (1999). [Results] A total of 69 patients were enrolled and treated, including 52 (75%) cases of follicular lymphoma (FL) and 11 (16%) cases of MCL, ages 33 to 75 years, with predominantly stage III/IV indolent B-NHL (86%) or MCL (64%). The median number of unique prior therapies was two (range, 1 to 16), and sixty-six patients (96%) had received rituximab as a prior therapy. Twenty-nine patients (42%) completed the planned six cycles of chemotherapy, with fifty patients (72%) receiving 3 or more cycles. Dose reduction of bendamustine was required in 11 patients (16%). The ORR was 91% (63 of 69 patients; 95% CI, 82% to 97%) with a complete response (CR) rate of 67% (%CR), including %CRu (46 of 69 patients; 95% CI, 54% to 78%). The ORR in FL and MCL was 90% and 100%, respectively. The %CR in FL and MCL was 66% and 73%, respectively. Median progression-free survival (PFS) for all 69 patients was not reached at the median follow-up duration of 248 days (39-359 days). Median PFS for indolent B-NHL (58) and MCL (11) patients was not reached at the median follow-up duration of 254 days and 226 days, respectively. Hematologic toxicities, including grade 4 lymphopenia (72%) and neutropenia (48%), were the most frequently reported toxicities in patients. Non-hematologic toxicities were mild, with no grade 4 non-hematologic toxicity recorded. The most frequently reported grade 3 non-hematologic toxicities were GI toxicities (9%) including grade 3 vomiting (4%) and anorexia (3%), and infections (7%) which included one case of grade 3 febrile neutropenia, pneumonia, herpes infection, and viral pharyngitis. [Conclusion] Bendamustine monotherapy is a highly effective and less toxic treatment in patients with relapsed or refractory indolent B-NHL and MCL who have been pretreated (96%) with rituximab. It is noteworthy that a very high complete response rate (73%) was achieved in relapsed or refractory MCL patients although the number of patients was relatively small. Disclosures: No relevant conflicts of interest to declare.

90Y Ibritumomab Tiuxetan (Y2B8, Zevalin®) Radioimmunotherap (RIT) Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin’s Lymphoma (B-NHL) Pretreated with Rituximab-Containing Chemotherapy (R-Chemo): Japanese Multicenter Phase II Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2767-2767 ◽  
Author(s):  
Michinori Ogura ◽  
Yasuo Morishima ◽  
Takashi Watanabe ◽  
Tomomitsu Hotta ◽  
Kennichi Ishizawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Bone Marrow Involvement ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Multicenter Phase ◽  
Highly Effective ◽  
Grade 3

Abstract Background and Objectives: Y2B8 RIT has been reported to be effective in patients with relapsed or refractory indolent B-NHL pretreated with rituximab monotherapy or chemotherapy. However, no data has been available for Y2B8 in indolent B-NHL pretreated with R-chemo. We conducted a multicenter phase II study of Y2B8 RIT to evaluate its efficacy and safety in patients with relapsed or refractory indolent B-NHL, focusing on those pretreated with R-chemo. Patients and Treatment: The Y2B8 regimen comprised an infusion of rituximab (250 mg/m2) and injection of 111In ibritumomab tiuxetan (In2B8) (3.5 mCi [129.5 MBq]) for imaging interpretation and estimation of the feasibility of Y2B8 administration, followed 1 week later by rituximab (250 mg/m2) and Y2B8 (0.4 mCi [14.8 MBq/kg] for platelets >150,000/μL or 0.3 mCi/kg [11.1MBq/kg] for 100,000/μL< platelets <150,000/μL). A total of 45 patients (32–72 years; median, 57 years) were enrolled: 66.7%, of stage III/IV at study entry; 82.2%, with follicular lymphoma; 33.3%, with bone marrow involvement; and 55.6%, with more than 2 prior therapy regimens (range, 1–11). Of them, 40 patients were treated with Y2B8: 22 with 0.4 mCi/kg and 18 with 0.3 mCi/kg. Two patients showed prominent bone marrow uptake on imaging inspection and did not receive Y2B8. Twenty-two patients were previously treated with R-chemo (18 R-CHOP, 2 R-COPP, 2 CHASER, 1 R-FAMP, and 1 R-EPOCH) and 15 patients had received rituximab monotherapy. Only 5 patients had not received rituximab. Results: The overall response rate was 83% (63% complete response [CR], 5% complete response unconfirmed [CRu], and 15% partial response [PR]), as evaluated by International Workshop Criteria modified by Japan Clinical Oncology Group. %CR in patients pretreated with R-chemo was 73% (78% in pts pretreated with R-CHOP). The median progression-free survival (PFS) time was 9.6 months (95% CI: 7.3 months to not calculated) with a median follow-up time of 6.5 months (range: 1.2–12.7 months). In complete responders, the median PFS has not been reached. Toxicity was primarily hematologic, transient, and reversible except in 2 patients, in whom prolonged grade 3 cytopenia and anemia did not recover by 6 months after the therapy (neutropenia and decreased Hb in one and thrombocytopenia in another). The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 43%, 5%, and 5%, respectively. No grade 4 non-hematologic toxicity was observed. Most frequent grade 3 non-hematologic toxicities were febrile neutropenia (4%), cystitis (4%), and pneumonia (4%). Conclusions: Y2B8 RIT is highly effective with acceptable toxicities in patients with relapsed or refractory indolent B-NHL. It is noteworthy that Y2B8 RIT brings high %CR in patients pretreated with R-chemo such as R-CHOP therapy.

The VcR-CVAD Regimen Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma (MCL): First Analysis of E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1661-1661 ◽  
Author(s):  
Brad S Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 1661 Poster Board I-687 Introduction One approach to improving outcomes in Mantle Cell Lymphoma (MCL) is to incorporate newer targeted agents into standard chemotherapy regimens. As the proteasome inhibitor bortezomib (Velcade‘) achieved a 33% response rate in relapsed MCL, we hypothesized that the incorporation of Velcade (Vc) into a modified R-hyperCVAD chemotherapy backbone would result in a high complete response rate (CR). The new regimen, VcR-CVAD, was tested for safety and efficacy in a phase II study within the Wisconsin Oncology Network (UW) and demonstrated a CR rate of 77% (Kahl, ASH 2008). To determine the safety and efficacy of this regimen in a cooperative group setting, we initiated E1405: a phase II study of VcR-CVAD with maintenance rituximab (MR) for untreated MCL. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0-2, and adequate end organ function. The treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1-3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1-2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1-4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients had an option to receive high dose chemotherapy and autologous stem cell transplantation (off protocol) rather than MR. The primary endpoint of the trial was the CR rate, incorporating PET imaging, to VcR-CVAD induction therapy. Results Seventy-six eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40-76), 59M:17F, 91% stage III/IV, and 39% with elevated LDH. Sixty-four patients (84%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), patient preference (2), and other/unknown (5). Response information is available on 74 patients while data is outstanding on 2 patients. The ORR was 96% (73/76; 95% CI, 89%-99%), CR rate 75% (57/76; 95% CI, 64%-84%) and the PR rate 21% (16/76; 95% CI, 13%-32%). Six of the PR patients were coded as such because of protocol violations in which a post-treatment bone marrow biopsy or PET scan was not obtained. The CR rate in the 68 completely restaged patients was 84%. Forty-four patients proceeded to planned MR while 21 patients went off protocol to SCT consolidation. Median follow up is currently too short (9 months) to assess PFS and OS. The major toxicity of the treatment regimen was expected myelosuppression. Grade 3-4 non hematologic toxicities were rare. No patients developed grade 3-4 neuropathy. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall response (96%) and CR rate (75%) in a representative MCL patient population treated on a cooperative group protocol. The CR rate was high and comparable to the UW pilot study (77%). No episodes of severe painful peripheral neuropathy were reported using the reduced vincristine dosage and the overall toxicity profile was very acceptable. Longer follow up is needed to determine if the high CR rate will translate into improved PFS and OS. Disclosures Kahl: Genentech: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as front line treatment in MCL. Smith:Genentech: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics, Inc.: Research Funding. Horning:Genentech: Honoraria, Research Funding.

Neoadjuvant combined modality therapy with weekly docetaxel (D) and cisplatin (P), 5-fluorouracil (5FU) continuous infusion (c.i.) and concurrent radiotherapy (RT) provides high pathological response rate in esophageal cancers (EC): A phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4057-4057 ◽  
Author(s):  
F. Pasini ◽  
G. De Manzoni ◽  
A. Grandinetti ◽  
C. Pedrazzani ◽  
C. Griso ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Combined Modality Therapy ◽  
Complete Response ◽  
Pathological Response ◽  
Hematological Toxicity ◽  
Weekly Schedule ◽  
Grade 3

4057 Background: The achievement of pathological complete response (pCR) is deemed essential to improve survival in EC. In a phase I study (Pasini et al, Ann Oncol 16; 1123, 2005) we demonstrated the feasibility of a novel protocol of neoadjuvant chemoradiation based on weekly D and P, c.i. of 5-FU and concurrent RT. Based on the promising results of the study, we then performed a phase II study aimed at evaluating pathological response rate and toxicity. Methods: 50 pts with stage II-III EC (26 adenocarcinomas) were enrolled (Simon test: P0=0.2, P1=0.6, alpha 0.05 beta 0.1; 54 pts); median age was 59 yrs (42–73). Treatment consisted of D 35 mg/m2 and P 25 mg/m2 d 1,8,15,29,36,43,50,57 plus 5-FU 180 mg/m2 c.i. d 1–21 and 150 mg/m2 c.i. d 29–64; concurrent RT (50 Gy) started on d 29. Surgery was performed 6 to 8 weeks after completion of RT. Results: 49/50 pts (98%) completed the planned chemo-radiation. Median follow-up is 22 mo (7–39). During chemo-radiation, grade 3–4 hematological toxicity occurred in 9 pts (18%)(4 pts grade 4) requiring GCSF support and postponement of CT of one week in 4. One HCV+ pt discontinued CT and continued with RT alone. In the last 2 weeks 12 pts (24%) experienced grade 3 non-hematological toxicities (asthenia, esophagitis, nausea) without need of treatment discontinuation. There was a fatal pulmonary embolism in a non neutropenic pt after completion of the therapy. 45 pts underwent surgery, while 5 did not (2 refusal). Pathological findings: pT0 pN0 (pCR): 25 (50%); pTrm pN0: 6 (12%)[residual microfoci]; pT2 pN0: 1 (2%); pT0–4 pN+: 9 (18% ); R+:4 ( 8%). Response rate was similar between adeno and squamous cell carcinoma. With a median follow-up of 24 mo, only 2 of 25 pCRs (8%) died (1 relapse, 1 postoperative death). Conclusions: i) a substantial pCR rate (50%) was achieved; ii) the weekly schedule allowed concomitant chemo-radiation at cumulative doses otherwise impossible with standard three weeks protocols; iii) because of the acceptable, but not negligible toxicity, this protocol requires to be managed in dedicated institutions. No significant financial relationships to disclose.

Pemetrexed (MTA) and carboplatin (CBDCA) in the treatment of advanced pleural mesothelioma (MPM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7093-7093 ◽  
Author(s):  
B. Castagneto ◽  
M. Mencoboni ◽  
D. Degiovanni ◽  
A. Muzio ◽  
L. Giaretto ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

7093 Background: Aim of this study was to evaluate the activity and toxicity of MTA and CBDCA combination as first line chemotherapy in advanced MPM. Methods: Chemonaive patients (pts) with histologically proven, an ECOG performance status (PS) 0–2, and measurable advanced MPM were considered. The schedule of administration was: pemetrexed 500 mg/m2 in combination with CBDA AUC 5, once every 21 days for 8 cycles. Results: From July 2003 to March 2005 76 pts (54 male and 22 female) have been treated with this combination chemotherapy. Median age was 62.7 years (range 40–70); median PS 0 (range 0–3); epithelial histologic findings were in 57 (75%), mixed in 13 (17.1%), sarcomatous in 3 (3.9%), and unspecified in 3 (3.9%) pts. A total of 537 cycles was administered (median 7, range 1 to 13). Grade 3 hematologic toxicity according to WHO criteria was seen in 43 (56.6%) pts (neutropenia in 30, thrombocytopenia in 8, and anemia in 5); grade 4 hematologic toxicity in 5 (6.6%) pts. The most common nonhematologic events were grade 3 nausea/vomiting in 10 (13.1%), and fever in 4 (5.3%) pts. 74 pts were evaluable for clinical response. There were 16 (21.%) partial responses (PR) and 3 (3.9%) complete responses (CR), for an overall response rate of 23.9%. 29 (38.2%) pts reported stable disease (SD). The overall survival was considered from date of diagnosis to date of death from any cause or to date of last follow-up. The median survival time for the entire group was estimated at 23 months. Conclusions: The results of this phase II study indicate that, at this dose and schedule, the combination of CBDCA and MTA is moderately active and that the profile of toxicity is acceptable in pts with advanced MPM. No significant financial relationships to disclose.

Phase II study of hydroxyurea for unresectable meningioma (Southwest Oncology Group S9811)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2063-2063 ◽  
Author(s):  
L. J. Swinnen ◽  
C. Rankin ◽  
E. J. Rushing ◽  
H. F. Laura ◽  
D. M. Damek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Disease Rate ◽  
Hematologic Toxicity ◽  
Benign Meningioma ◽  
Small Series ◽  
Grade 3

2063 Background: Meningiomas account for 15%-18% of CNS tumors. Although benign, recurrence is seen in 16%-39% of cases, depending on the extent of resection possible. Tumor location may make further resection hazardous. Chronic hydroxyurea (HU) was reported to produce well documented objective responses in a small series of patients, with gradual regression occurring over 6–10 months. Induction of apoptosis was furthermore demonstrated with HU in primary benign meningioma explant cultures. The S9811 phase II trial was undertaken to estimate the objective response rate, if any, of unresectable benign meningioma to this HU regimen. Methods: Eligibility required unresectable, measurable, residual or recurrent, histologically-proven benign meningioma. Progressive tumor or progressive neurologic deficit was required. No prior cytotoxics, no radiation therapy for >1 year. Age > 18, adequate hematologic reserve, PS 0–2. HU 20 mg/kg/day po was given for up to 2 years if there was no progressive disease. Single-stage accrual of 38 pts would have allowed detection of 5% null hypothesis response probability vs. 20% with 90% power; the 28 pts actually accrued provide 81% power. Results: Between November 98 and June 2005, 29 pts were accrued, with study closure due to slow accrual. 1 ineligible. Response assessment showed CR+PR 0% (95% CI 0–12%); SD 71% (95% CI 51–87%); PD 21% (95% CI 8–41%); undetermined 7%. Median PFS was 27 months. (95% CI 12–29 months.); 3-year PFS 43% (95% CI 25–61%). Median OS has not been reached. Seven patients were removed from study for toxicity (5/7 hematological). Toxicity was mainly hematologic: 11/28 (39%) grade 3, 2/28 (11%) grade 4. Grade 3 non-hematologic toxicity was seen in 7/28 (25%). Conclusions: Chronic HU therapy for unresectable benign meningioma resulted in an estimated objective response rate of < 12%. Whether the stable disease rate seen differs in any way from what can be expected from the natural history of meningioma cannot be determined from this phase II study design. No significant financial relationships to disclose.

Phase II study of topotecan and carboplatin in the treatment of platinum-sensitive recurrent ovarian and peritoneal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15001-15001
Author(s):  
P. Hanjani ◽  
M. S. Shahin
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Peritoneal Cancer ◽  
Platinum Sensitive ◽  
Free Interval ◽  
Alive With Disease ◽  
Grade 3

15001 Background: The aim of this trial was to investigate the efficacy and toxicity of the combination of Topotecan (T) and Carboplatinum (C) in the management of recurrent platinum sensitive ovarian and peritoneal cancer. Methods: T (1 mg/m2) was given as a 30-minute infusion daily × 3 days and C (AUC 5) was given as a 30-minute infusion following T on day 3 on a 21-day cycle. Results: Thirty patients (pts) were enrolled and all pts were evaluable for response and toxicity. Mean age was 63.2 (range = 44–84). One hundred eighty five cycles (mean/pt = 6, range 2–10) were evaluable for toxicity. Dose escalation (T = 1.25 mg/m2) was possible in 25 (83.3%) pts. Hematologic toxicity grade 3 and 4 neutropenia was seen in 60 (32.4%) and 10 (5.4%) cycles, respectively. Grade 3 thrombocytopenia was encountered in 24 (13%) cycles. Grade 3 Hgb was observed in 4 (2.2%) cycles. No grade 4 thrombocytopenia/Hgb or neutropenic fever was encountered. Blood transfusions were required in 9 (4.9%) cycles. Bone marrow support with erythropoiten (40% pts), and filgrastim (43.3% pts) were utilized. No neuropathy > grade 1 was encountered. Fourteen pts (46.6%) pts had a hypersensitivity reaction to C and successful desensitization was carried out in 8 (57.1%). Mean follow-up interval was 16.9 months (mos) (Range 1.7–43). To date, 6 (20%) pts are alive without disease, 16 (53.3%) are alive with disease, and 8 (26.7) have died of disease. The overall response rate was 83.3% (5 CR and 20 PR). Five (16.6%) pts had SD. Median progression-free interval was 8.2 mos. Overall mean survival for the cohort was 31.2 mos (95% CI: 24.47–37.71). Conclusions: Given the ICON-4 data, supporting combination therapy in recurrent platinum-sensitive patients, this regimen provides an effective and tolerable alternative to Taxane-platinum combination with no significant neuropathy. This regimen is especially attractive in patients who have significant residual neuropathy after initial treatment. Carboplatinum desensitization was feasible in previously pre-treated patients. No significant financial relationships to disclose.

A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4550-4550 ◽  
Author(s):  
H. Ueno ◽  
T. Okusaka ◽  
J. Furuse ◽  
K. Yamao ◽  
A. Funakoshi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Good Survival ◽  
Multicenter Phase ◽  
Grade 3

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.

Multicenter phase II study of FOLFOX or biweekly XELOX and cetuximab as first-line treatment in patients with wild-type KRAS/BRAF metastatic colorectal cancer (mCRC) (FLEET study).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 463-463
Author(s):  
Ho Min Kim ◽  
Hitoshi Soda ◽  
Shoichi Hazama ◽  
Takao Takahashi ◽  
Naoki Nagata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Predictive Biomarker ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Few Data

463 Background: Cetuximab and chemotherapy as first-line therapy for patients with KRAS wild type prolong survival. However, COIN trial has not demonstrated the survival benefit of FOLFOX or XELOX and cetuximab therapy. Few data are available on its benefit for patients with KRAS and BRAF wild-type. Methods: The aim of this study was to assess the efficacy of first-line FOLFOX or bi-weekly XELOX and bi-weekly cetuximab in KRAS/BRAF wt mCRC. Chemonaive patients received FOLFOX or biweekly XELOX (oxaliplatin 85 mg/ m2/day 1 plus capecitabine 2000/m2/days 1-7) and biweekly cetuximab 500mg m2/ day 1 every 2 weeks. Primary endpoint was response rate(RR), other secondary endpoints were PFS, OS, DCR, safety, DI and resection rate. KRAS test (codon12,13) and BRAF test (V600E) by direct sequence were performed in Yamaguchi University. Patients with KRAS/BRAF wt were enrolled in this study. The regimen of FOLFOX or XELOX were selected by investigator’s preference, not randomized. Results: From April 2010 to May 2011, 139 pts were preregistered. KRAS and BRAF were examined from paraffin-embedded sample. 70 (50.3%) pts were KRAS/BRAF wt, and 62 pts were enrolled: The main characteristics of the entered pts were: sex (M/F) 34/28, median age 66 yrs (range 34-83 yrs). Grade 3/4 adverse events were leucopenia 4.8%, neutropenia 25.8%, skin toxity (paronychia/fissure) 9.7%, and acne 9.7%. Two CR (3.2%) and 40 PR (64.5%), 15 SD (24.2%) and 3 PD (4.8%) 2NE were observed, with an overall response rate of 67.7% and a disease control rate (CR+PR+SD) of 91.9%. The RR of FOLFOX or XELOX were 64.9% (24/37) and 72.0% (18/25), DCR were 89.2% and 96% respectively. Conclusions: FLEET was the first multicenter phase II study with prospective KRAS/BRAF analysis as a predictive biomarker for cetuximab in first-line mCRC in Japan. Results of this study indicate that both biweekly combination regimens are feasible, tolerable, and clinically active. Biweekly XELOX+cetuximab study (FLEET2) is ongoing. Clinical trial information: UMIN000003253.

Results of a Phase II Study of 506U78 (Nelarabine) in Refractory Indolent B-Cell or Peripheral T-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2681-2681 ◽  
Author(s):  
Michael A. Thompson ◽  
Barbara Pro ◽  
Andreas Sarris ◽  
Fredrick B. Hagemeister ◽  
Andre Goy ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Single Agent ◽  
Complete Response ◽  
Water Soluble ◽  
Adult T Cell Leukemia ◽  
Grade 3

Abstract BACKGROUND: Compound 506U78 (Nelarabine), a water soluble pro-drug of 9-β-d-arabinofuranosyl-guanine, is demethoxylated by adenosine deaminase to ara-G in lymphoblasts. Intracellular ara-G is then phosphorylated via deoxycytidine kinase and mitochondrial deoxyguanosine kinase to its active 5′-triphosphate, ara-GTP. Ara-GTP, a potent inhibitor of DNA polymerase, also incorporates into DNA resulting in cell death. Studies in children and adult T-cell leukemia and non-Hodgkin’s lymphoma (NHL) have shown activity, but with reversible neurotoxicity as the most prominent adverse event. METHODS: We report here the results of a phase II study with 506U78 in adults (median age 64, range 33–81) with relapsed or refractory indolent B-cell or peripheral T-cell NHL. Patients had received a median of 2 prior courses of chemotherapy. 506U78 was given at 1.5 g/m2/day IV on days 1, 3, and 5 every 28 days to a maximum of 6 cycles unless toxicity or progressive disease. If after 4 cycles a complete response (CR) or partial response (PR) was not achieved, then treatment was discontinued. RESULTS: There were 23 patients enrolled including 13 with T-cell and 10 with indolent B-cell NHL. Among 19 assessable for response, the overall response rate (ORR) in T-cell NHL was 4/9 (44%) with 2 CR and 2 PR, while in indolent B-cell NHL the PR was 3/9 (33%) with no CR. In responders, the median time to progression (TTP) was 8 months (range 2–22 months). Sixteen of 22 (73%) patients evaluable for toxicity had grade 3 or 4 adverse events. Neurotoxicity included one grade 3 and one grade 4 event. CONCLUSION: Compound 506U78 is active as a single agent in T-cell and B-cell NHL. Our response rate was higher than the ORR of 10.5% reported previously in the Czuczman et al. (2004) Blood 104(11) abstract in adults with T-cell NHL and there was less neurotoxicity in our study. This may be related to different dosing regimens (every 28 days vs. every 21 days). Compound 506U78 should be further evaluated in clinical trials.

Bendamustine, Bortezomib and Dexamethasone (BVD) in Patients with Relapsed-Refractory Multiple Myeloma (MM): Updated Results of a Multicenter Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4734-4734
Author(s):  
Massimo Offidani ◽  
Laura Maracci ◽  
Laura Corvatta ◽  
Liberati Anna Marina ◽  
Stelvio Ballanti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Prior Treatment ◽  
New Drugs ◽  
Induction Phase ◽  
Grade 3 ◽  
Therapy Reduction

Abstract Introduction: Bendamustine, a bifunctional alkylating agent, exerts a mechanism of action different from that of other conventional alkylators despite it remains mostly unknown. In patients with newly diagnosed or relapsed-refractory MM bendamustine has proven to be active either as monotherapy or in combination with new drugs, particularly bortezomib and immunomodulatory agents. Methods: The preliminary results of this prospective, phase II study conducted in 22 Italian centres are recently published (Blood Cancer J. 2013, 3: e162). Here we present the conclusive results of the combination Bendamustine (70 mg/m2 days 1, 8), Bortezomib (1.3 mg/ m2 days 1, 4, 8, 11) and Dexamethasone (20 mg days 1-2, 4-5, 8-9, 11-12) (BVD) administered every 4 weeks in patients with relapsed-refractory MM of any age, with adequate cardiac, liver and hematological function, not refractory to bortezomib and treated with no more than four previous lines of therapy. The primary endpoint of this study was achievement of a response at least PR, as to IMWG criteria, after four cycles of BVD. Patients achieving a response less than a PR were taken off-study. Patients obtaining at least a PR received two additional treatment cycles followed by a 12-months consolidation phase with cycles repeated every 2 months. Therefore, patients with a PR after the induction phase could receive up to 18 months of treatment and up to 12 cycles of BVD. Results: 75 patients were included in the study. Median age was 68 years (range 41-85 years), 26.5% had ISS stage 3, 19% IgA myeloma and 9% renal failure. Eight of 36 evaluable patients (22%) had high-risk cytogenetics. Patients had received a median of one prior line of therapy (range 1-4). All patients had received prior treatment with new drugs, such as thalidomide (57%), lenalidomide (54.5%), bortezomib (46.5%) or both (20%). Twenty-four patients (32%) were refractory to IMIDs. Best response rate was 75%, including 14 CRs (20%), 22 VGPRs (24%) and 27 PRs (31%). Five patients (6.5%) died early. Only prior treatment with bortezomib significantly reduced the response rate ≥ PR (48.5% vs 80%; P = 0.004). At a median follow-up of 27 months (range 18-38), 45 patients had progressed and 43 had died. Median TTP and PFS were 17 and 12.5 months, respectively while median OS was 24 months (40% at 3 years). After longer follow-up, prior therapy with bortezomib plus lenalidomide was confirmed as the only factor that significantly reduced TTP (9 vs 19 months; HR = 2.7; 95% CI = 1.3-5.8; P = 0.009), PFS (9 vs 15 months; HR = 2.1; 95% CI = 1.2-3.8; P = 0.020) and OS (17 vs 32 months; HR = 2.1; 95% CI = 1.2-3.9; P = 0.043). Grade 3-4 adverse events occurred in 55% of patients leading to therapy reduction in 24% and to protocol discontinuation in 11% of patients. The most frequent severe adverse events were thrombocytopenia (28%), neutropenia (20%), infections (12%), peripheral neuropathy (9%), gastrointestinal (5%) and cardiovascular events (4%). Compared with younger, patients aged > 70 years had a significantly higher incidence of grade 3-4 side effects particularly thrombocytopenia and infections with, consequently, a higher rate of therapy reduction and discontinuation. Moreover, 4/5 early deaths occurred in patients aged more than 70 years. Conclusions: BVD combination is an effective and well tolerated regimen in relapsed-refractory MM. Data suggest that the optimal target of BVD maybe patients younger than 70 years who has not previously received both bortezomib and lenalidomide. Disclosures Offidani: Mundipharma, Janssen: Honoraria. Off Label Use: Bendamustine. Corvatta:Janssen: Honoraria. Ballanti:Janssen: Honoraria. Brunori:Janssen: Honoraria.

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