Final Results of a Phase II Study of Bortezomib (Velcade) in Combination with Liposomal Doxorubicin (Doxil) and Thalidomide (VDT) Demonstrate a Sustained High Response Rates in Patients (pts) with Relapsed (rel) or Refactory (ref) Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3539-3539 ◽  
Author(s):  
Asher Alban Chanan-khan ◽  
Swaminathan Padmanabhan ◽  
Kena C. Miller ◽  
Laurie Musiel ◽  
Jihnhee Yu ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Phase Ii ◽  
Survival Data ◽  
Low Dose ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Response Rates ◽  
High Response ◽  
Cell Transplant ◽  
Salvage Regimen

Abstract Background: Tumor microenvironment (ME) plays an important role in MM. It is associated with disease progression, metastasis, and resistance to therapy. Therefore, targeting the ME and the tumor cell simultaneously may be an effective way to overcome resistance in pts with rel/ref MM. Aim: Orlowski et al reported improved anti-tumor responses when bortezomib (V) was combined with doxil (D) in pts with hematologic malignancies. We investigated clinically, this approach i.e., targeting the MM cell as well as its ME, using a combination of V, D and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Here we report the final results along with survival data of this phase II study. Methods: All pts with rel/ref disease were eligible for this study. V was given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4–6 cycles. SWOG criterion was used to assess response. Low-dose coumadin (1–2 mg po qd) was used for prevention of venous thromboembolism (VTE). Results: Twenty three pts (9M, 14F; median age −57 , range 43–79 yrs; 21MM, 2 WM) have been enrolled. All pts had Stage III disease, median b2M was 4.2 and median number of prior therapies were 5(range 1–6). Prior therapies included stem cell transplant(SCT) in (41%), T (41%), adriamycin(A) (65%) steroids (82%) and velcade (12%). 74% had refractory disease. Seventeen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken off study for non-compliance after 1 cyc. ORR was with 65%(CR+PR) with 23% CR all of whom were IFE negative. The Median Progression Free survival was 10.9 months with an median overall survival of 15.7 months. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. No significant non-hematologic Gr. III/IV toxicity were seen. Despite prior exposure to anthracycle, we did not noted any cardiotoxicity with D.No significant neuropathy was noted. Conclusions: Pt with rel/ref MM usually have aggressive disease with paucity of effective regimens. VDT is an effective salvage regimen. Final results show high response rates with 22% of the patients achieving complete (IFE−) remissions. Responses were noted regardless of type of prior therapy. VDT could be safely given in patients with renal failure/insufficiency. Venous Thromboembolism (VTE) does not appear to be a problem with low dose coumadin prophylaxis. Final results of this phase II study will be presented at the 48 th annual ASH meeting.

A Phase II Study of Velcade (V), Doxil (D) in Combination with Low-Dose Thalidomide (T) as Salvage Therapy for Patients (pts) with Relapsed (rel) or Refractory (ref) Multiple Myeloma (MM) and Waldenstorm Macroglobulinemia (WM): Encouraging Preliminary Results.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2421-2421 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Kena C. Miller ◽  
Philip McCarthy ◽  
Laurie A. DiMiceli ◽  
Jihnee Yu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Salvage Therapy ◽  
Low Dose ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Synergistic Activity ◽  
Salvage Regimen ◽  
Highly Active ◽  
Development Of Resistance

Abstract In MM, tumor microenvironment (ME) plays an important role in disease progression, dissemination, and development of resistance to therapy. Pts with rel/ref MM have limited treatment options. Therefore, targeting the ME simultaneously with malignant cells may be an effective way to overcome resistance in pts with rel/ref MM. Orlowski et al recently reported synergistic activity of V+D in patients with hematologic malignancies. A phase II trial initiated at our institute is exploring this approach, targeting the MM cell as well as its ME, using a combination of Velcade (V), Doxil (D) and low-dose thalidomide (T) as salvage therapy for pts with rel/ref MM. Pts with rel/ref disease are eligible for this study. V is given at 1.3mg/m2 (D1,4,15,18) and D at 20mg/m2 (D1,15) every 4 weeks with daily T (200 mg) for 4–6 cycles. SWOG criterion was used to evaluate response. Low-dose coumadin (1–2 mg po qd) was used for prevention of venous thromboembolism (VTE). Eighteen pts (7M, 11F; median age 56, range 44–80 yrs; 16MM, 2 WM) have been enrolled to date. All pts had Stage III disease, median b2M of 4.8 (nl range: 0–2.15) and median prior therapies 2 (range 1–7). Prior therapies included stem cell transplant in (46%), T (54%), adriamycin(A) (70%) and steroids (92%). Thirteen pts have completed at least 1 cyc and are available for toxicity and response evaluation. One pt died of sepsis prior to completing 1 cyc and 1 pt with PR was taken of study for non-compliance after 1 cyc. ORR was 100% (13/13) with 5PR and 8MR. All pts are currently continued on therapy. Toxicity: 2 pts developed Gr. II plantar-palmar erythrodysthesia (PPE) and 1 had Gr. III cellulitis. No VTE was noted. VDT is a highly active salvage regimen in pts with rel/refr MM. Responses were noted despite prior failure of steroids, T or A. It is well tolerated without any significant non-hematologic Gr. III/IV toxicity. VTE does not appear to be a problem. Updated results of this first cohort of pts will be presented at the annual ASH meeting.

A phase II study of cetuximab (cet) and mFOLFOX6 in metastatic colorectal cancer (mCRC) (JACCRO CC-05).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 611-611
Author(s):  
Tatsuro Yamaguchi ◽  
Akihito Tsuji ◽  
Yu Sunakawa ◽  
Masato Nakamura ◽  
Mitsugu Kochi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Base Line ◽  
First Line ◽  
Treatment Regimens ◽  
Chronological Change ◽  
Recommended Treatment

611 Background: FOLFOX4 combined with cet for mCRC patients (pts) with KRAS wild tumor demonstrated the prolonged progression-free survival (PFS) with higher response rate (RR) in the OPUS study. To evaluate the clinical efficacy and safety of the cet plus mFOLFOX6, we conducted a multi-center phase II study of Japanese pts. Methods: In this trial, pts with KRAS wild type tumor and receiving no prior chemotherapy for mCRC were treated with cet (initial dose 400, and 250 mg/m2 weekly) followed by mFOLFOX6 (oxaliplatin 85mg/m2, l-leucovorin 200 mg/m2, fluorouracil, as 400mg/m2 intravenous bolus then 2,400mg/m246-hour continuous infusion). The treatment was repeated every 2 weeks. The primary endpoint was RR evaluated by the external review board according to RECIST v1.1. Secondary endpoints included PFS, OS, % chronological change at the base line and safety. Results: A total of 57 pts were enrolled from August 2010 to September 2011. The median age was 60 years, 65% of pts were male, and ECOG PS 0 was observed in 91% of pts. All pts had EGFR-expressing disease. The median treatment courses were 21 (cet) and 10 (FOLFOX). The RR was 66.7% (95%CI, 53.4 to 77.7). Complete remission was observed in 5 cases (9.3%). The median PFS was 11.1 months (95%CI, 8.0 to 14.7). The early tumor shrinkage (ETS; over 20% regression at 8 weeks) was observed in 80% of pts, and the PFS for pts with ETS was statistically significantly prolonged as compared with pts without ETS (median PFS, 11.5 vs. 3.7 months, respectively; p = 0.0002). The OS was not reached at the time of median follow-up (19.2 months). Grade 3 or worse adverse events were neutropenia (48.2%), leucopenia (22.2%), rash acneform (20.4%), and peripheral neuropathy (18.5%). Conclusions: The first-line cet+mFOLFOX6 has an acceptable safety profile and demonstrates advantages in response rate for pts with KRAS wild tumor. The first-line cet+mFOLFOX6 should be considered as one of the recommended treatment regimens for pts with KRAS wild tumor. Update survival data will be presented. Clinical trial information: UMIN000004197.

An update on gemcitabine, rituximab, and oxaliplatin in combination for relapsed/refractory non-Hodgkin lymphomas.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8084-8084
Author(s):  
Robert M. Crescentini ◽  
Kendra Lynn Sweet ◽  
Jijun Liu ◽  
Idalia Liboy ◽  
Samir Dalia ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Salvage Regimen ◽  
Bulky Disease ◽  
Grade 3 ◽  
Large B Cell

8084 Background: Relapsed/refractory non-Hodgkin lymphomas (NHL) have no standard of care. A variety of salvage chemotherapy options are available. We previously reported results of our phase II trial using gemcitabine, rituximab and oxaliplatin (GROC) in the salvage setting for relapsed/refractory NHL in which we observed an overall response rate of 58% with an incidence of grade 3-4 thrombocytopenia of 9% and neutropenic fever of 3.5%, but no grade 3-4 non-hematologic toxicities. Here we update progression free survival (PFS) and overall survival (OS) data. Methods: This phase II, single-arm, multicenter study evaluated safety and efficacy of GROC in patients with relapsed/refractory NHL. Patients were treated on a 14 day cycle. On day 1, patients with CD20+ NHL received rituximab (375 mg/m2). On day 2, patients received gemcitabine (1000 mg/m2) and oxaliplatin (100 mg/m2). Granulocyte colony stimulating factor was given. Stem cell transplant (SCT) was considered after a minimum of 6 cycles. Results: A total of 58 patients were enrolled from the H. Lee Moffitt and the Auxilio Mutuo Cancer Centers. Ages ranged from 24 to 88 years (median 72 years). The majority of patients had an ECOG performance status of 0-1 (89%). Lymphoid neoplasms included large B-cell (79%), follicular (7%), lymphoblastic (1.8%), Burkitt (1.8%), primary mediastinal large B-cell (3.5%), and peripheral T-cell lymphoma (7%). Eighty-one percent of patients had stage III-IV disease, median IPI was 3, 40% had B-symptoms, 43% had bulky disease and 74% had an elevated LDH. Anthracycline-based therapy had been used in 91% of patients and 66% had received rituximab. Median PFS was 134 days (95% CI 115-153) and median OS was 296 days (95% CI 164-428). No difference in response was observed based on age >60, IPI, LDH or albumin levels. Prior therapy with rituximab (p=0.02) and initial response to front-line therapy (p=0.04) appear to correlate with improved outcomes. Nine patients went on for SCT. Conclusions: GROC is a useful salvage regimen for relapsed/refractory NHL with minimal toxicities and good clinical efficacy. Several patients were able to be successfully mobilized, collected and transplanted post GROC therapy.

A multicenter phase II study of bendamustine with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8023-8023 ◽  
Author(s):  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Nozomi Niitsu ◽  
Seok Jin Kim ◽  
Ken Ohmachi ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Salvage Regimen ◽  
Prior Therapy ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

8023 Background: Effective salvage therapies are needed in patients (pts) with relapsed/refractory DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, including DLBCL. This phase II study assessed the efficacy and safety of B-R in pts with relapsed/refractory DLBCL. Methods: Pts with histologically confirmed DLBCL (excluding transformed disease) and 1-3 prior therapies received rituximab 375 mg/m2 IV on day 1 and bendamustine 120 mg/m2 IV on days 2 and 3 of each 21-day cycle, for up to 6 cycles. Recovery of neutrophil count to ≥1,000/mm3 and platelet count to ≥75,000/mm3 were required prior to the start of each cycle; treatment delays >2 weeks resulted in discontinuation. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and safety. Results: A total of 63 pts were enrolled; data from 59 pts were available. Median age was 67 (range, 36-75) years with 37 pts over 65 years. The majority of pts (64.4%) had 1 prior therapy; 57 pts (96.6%) were previously treated with rituximab-containing combination chemotherapy and 8 (13.6%) had prior auto-PBSCT. Pts received a median of 4 (range, 1-6) treatment cycles. Sixteen (27.1%) pts completed 6 treatment cycles; most common reasons for early discontinuation were disease progression (n=15) and failure to meet criteria to start the next cycle (n=13). Among 59 pts evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109-410). Most common grade 3/4 adverse events (AEs) included CD4 lymphocytes decreased (66.1%), neutropenia (54.2%), and thrombocytopenia (10.2%). Four (6.8%) pts discontinued due to serious AEs (cytomegalovirus infection, infection, pneumonia, and pneumonia/respiratory failure). Conclusions: B-R demonstrated promising activity in pts with relapsed/refractory DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for pts with relapsed/refractory DLBCL after R-CHOP.

Imatinib plus hydroxyurea in pretreated nonprogressive glioblastoma (GBM): Long-term follow up of a single-center phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13004-e13004
Author(s):  
Gregor Paul Dresemann
Keyword(s):  
Dose Reduction ◽  
Phase Ii ◽  
Survival Data ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Continuous Treatment ◽  
Term Survival ◽  
Cell Counts

e13004 Background: GBM is malignant brain tumour with a median survival of 15.6 months. Dysregulated signalling of platelet derived growth factor receptors is suggested to play a role in pathogenesis. The combination of imatinib (I) plus hydroxyurea (HU) is known to be well tolerated and to show moderate efficacy in patients (pts) with recurrent GBM. Despite the aggressive course of GBM once starting progression, short periods of disease stabilisation after primary treatment or effective treatment of relapse can be observed. This Phase II study was initiated to analyse the efficacy of I plus HU as maintenance treatment (MT) in GBM pts. Methods: From December 2003 up to June 2005 30 pts were included. No enzyme-inducing anticonvulsive drugs were allowed. I (600 mg/day) and HU (1000 mg/day) were given as a continuous treatment. Blood cell counts were taken weekly and magnetic resonance imaging every 6 weeks. Primary endpoint (PE) was 6 and 12 months progression free survival (PFS), secondary endpoints (SE) were 5 years PFS and overall survival (OS). Results: All pts were eligible for PE and SE. 25 pts were male, 5 pts female, median age was 44 years (32 to 71). All pts had prior irradiation, 21 pts had prior temozolomide (T) containing therapy and 9 pts non-temozolomide containing therapy. 8 pts had none, 17 pts one and 5 pts two prior relapses. 25 pts had measurable disease, 4 of these pts achieved a partial response (PR), there was no complete remission, 5 pts had no evidence of disease. Median follow up is 90 months. Hematotoxicity grade 2 and 3 occurred in 11 out of 30 pts and required dose reduction of HU in 8 pts, dose reduction of I in 1 patient and G-CSF in 8 pts. PFS rate at 6, 12, 24 and 60 months were 60% (18/30), 40% (12/30), 17% (5/30) and 17% (5/30 ) respectively, OS rate at 6, 12, 24 and 60 months were 90% (27/30), 67% (20/30), 37% (11/30) and 17% (5/30). 4 pts are still alive without progression. Conclusions: Although I and HU did not demonstrate relevant efficacy in GBM and never reached admission status the reported study indicates impressive long-term survival data for I and HU as a continuous oral MT. Further studies should analyse more effective drugs like temozolomide as MT (proof of principle). Clinical trial information: STI571DE21.

Age under 40 Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transplant Despite High Response Rates.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5123-5123
Author(s):  
Parneet K. Cheema ◽  
Sahar Zadeh ◽  
Donna Reece ◽  
Christine I. Chen ◽  
Suzanne Trudel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Young Patients ◽  
Progression Free Survival ◽  
Response Rates ◽  
High Response ◽  
Clinical Feature ◽  
High Dose ◽  
Young Cohort ◽  
Cell Transplant

Abstract BACKGROUND: Multiple myeloma (MM) only occurs in 2% of patients under the age of 40. It has been reported that this young cohort of patients have a superior overall survival when compared to those over the age of 40. OBJECTIVE: To evaluate the clinical and laboratory features of patients ≤40 years of age at diagnosis of MM and to compare survival outcomes to patients >40 years of age. METHODS: Retrospective institutional review of all patients ≤40 years of age at time of diagnosis of MM that had underwent upfront ASCT at PMH from January 1, 1990 to July 31, 2007. Outcomes were compared to patients >40 years of age who had also undergone ASCT as upfront therapy. RESULTS: 37 patients ≤40 years of age were identified. Twenty patients were male. Immunoglobulin subtype was as follows: 49% had IgG, 19% light chain,16% IgA, 8% IgD, and 5% IgG plasma cell leukemia. The main presenting clinical feature was bone pain (63%). 73% had radiological evidence of bony disease at diagnosis and 53% of these patients required radiation prior to ASCT. Clinical features included anemia in 81%, renal insufficiency in 39% and hypercalcemia in 28%. Conditioning regimens for ASCT were high dose melphalan (200mg/m2) alone in 25 pts, VP-16 & melphalan +/− TBI in 8 pts, bleomycin & cyclophosphamide in 3 pts, and in 1 pt it was unknown. Median time to engraftment of neutrophils (>0.5 x 109/L) and platelets (>20 x 109/L) was 11 days (range 8–18) and 12 days (range 0–54), respectively. Median duration of hospitalization was 17 days (range 10–54). No treatment related mortality was experienced. Response to ASCT was as follows in 29 evaluable pts: CR in 10 (34.5%), PR in 13 (44.8%), MR in 1 (3.4%), SD in 3 (10.3%), and PD in 2 (6.9%). Five patients underwent a tandem ASCT. Maintenance therapy was instituted in 11 pts. Median progression free survival (PFS) post ASCT was 23.0 months, which is similar to the PFS of 28.5 months in patients over 40 (p=0.559). There was also no difference in median overall survival (OS) from date of ASCT between the two groups (6.6 years in pts ≤40, 6.7 years in pts >40; p=0.797). CONCLUSION: Young patients with MM present with advanced disease as evidenced by anemia, bone involvement and hypercalcemia. ASCT yields high response rates, but PFS post ASCT is less than 2 years. Although young age has been historically been considered to be a positive prognostic marker, OS post ASCT is only 6.6 years, which is equivalent to those >40 years of age. Strategies to better the outcomes of young patients with MM are required.

A Phase II Study of Pegylated Liposomal Doxorubicin (PLD), Bortezomib, Dexamethasone and Lenalidomide (DVD-R) for Patients with Relapsed/Refractory (R/R) Multiple Myeloma (MM)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3044-3044
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Alan D. Cartmell ◽  
Thomas B. S. Woliver ◽  
Marshall S. Flam ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Response Rates ◽  
High Response ◽  
Hand Foot Syndrome ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 3044 Background: Despite the availability of many new therapeutic options showing efficacy for R/R MM patients, many of these treatments produce significant side effects and the disease remains incurable. The combination of PLD and bortezomib has shown significant anti-MM efficacy leading to FDA approval of that combination for patients who have received one prior therapy and are naïve to bortezomib. Moreover, the combination of lenalidomide and dexamethasone has also been approved for patients who have received one prior regimen. However, both regimens are associated with significant toxicity and produce response rates in only 40–60% of patients. Previous studies in our laboratory show the increased efficacy and improved tolerability of PLD given daily compared to weekly administration in severe combined immunodeficient mice bearing human MM. Based on these results and the frequent occurrence of peripheral neuropathy with bortezomib when given at 1.3 mg/m2 dose on days 1, 4, 8, and 11 of a 3-week schedule, we modified the doses and schedules of both drugs and added intravenous (i.v) dexamethasone for MM patients. Using a modified lower dose (1.0 mg/m2) and longer cycle (4 weeks) of bortezomib administered on days 1, 4, 8, and 11 with lower dose PLD and intravenous (i.v.) dexamethasone administered on the same days for MM patients in both the frontline and R/R setting, we have shown the efficacy and marked reduction in AEs including neuropathy, hematologic, and hand-foot syndrome. A recent phase I/II trial investigating the combination of higher doses of lenalidomide, bortezomib, oral dexamethasone, and PLD on a 3-week schedule for newly diagnosed MM patients showed a high response rate but was associated with frequent AEs. Methods: Thus, we conducted a single-arm multi-center phase II study for R/R MM patients to evaluate the combination of i.v. dexamethasone, bortezomib, PLD, and lenalidomide. The treatment consisted of 40 mg dexamethasone followed by 1.0 mg/m2 bortezomib and then 4.0 mg/m2 PLD on days 1, 4, 8, and 11 of a 28-day cycle. Lenalidomide was administered orally at a dose of 10 mg daily on days 1–14 of each cycle. Patients were treated to a maximum response plus two additional cycles or completed a maximum of eight cycles of therapy without disease progression. Results: Eighteen (of 40 planned) patients have been enrolled to date with a median age of 72 years (range, 34–82 years). Patients were heavily pretreated with a median of 4 (1-17) prior regimens. Sixteen (89%) patients received prior bortezomib and 11 (61%) were previously treated with either doxorubicin or PLD. Seven (39%) of these patients were exposed to both drugs. Fifteen (83%) had received prior glucocorticoids. Nine (50%) individuals had received immunomodulatory agents with 6 (33%) having been exposed to lenalidomide and all 9 to thalidomide. The majority of patients (72 %) showed International Staging System II or III disease. To date, 16 patients (89%) have shown objective responses to the DVD-R regimen, including 1 complete response (6%), 5 very good partial responses (28%), 4 partial responses (22%) and 6 minimal responses (33%). One of the nonresponding patients showed stable disease and the other progressed after one cycle of therapy. Thus, disease control was achieved in all but one patient (94%). To date, 6 patients have shown progressive disease after a median follow-up time of 6 months (1+ - 9+ months). The DVD-R regimen was well tolerated and only one patient discontinued treatment because of toxicity (peripheral neuropathy). Ten patients experienced grade 3 or 4 adverse events. The most common grade 3 adverse events were reversible neutropenia (n=3), pneumonia (n=3), reversible anemia (n=2), and thrombocytopenia (n=2). There were two patients with grade 4 thrombocytopenia that was reversible. To date, 5 patients (28%) have developed treatment-emergent peripheral neuropathy (four grade 1 and one grade 3). Notably, there have been no cases of stomatitis or hand-foot syndrome. Conclusions: Thus, these results suggest that the DVD-R regimen using a modified schedule and doses of the combination of intravenous dexamethasone, bortezomib, PLD and lenalidomide is a well tolerated treatment that produces high response rates for heavily previously treated MM patients with R/R disease. Disclosures: Berenson: Millennium: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Centocor OrthoBiotech: Consultancy. Vescio:Millennium: Speakers Bureau; Celgene: Speakers Bureau. Swift:Millennium: Consultancy.

Phase II study of antiangiogenic (metronomic) chemotherapy for recurrent malignant gliomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1569-1569 ◽  
Author(s):  
S. Kesari ◽  
D. Schiff ◽  
L. Doherty ◽  
D. Gigas ◽  
T. Batchelor ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Study ◽  
Malignant Gliomas ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Angiogenesis Inhibitors ◽  
Anaplastic Gliomas ◽  
Prevent Tumor Growth

1569 Background: There is preclinical evidence that continuous low-dose chemotherapy may inhibit tumor endothelial proliferation and prevent tumor growth (Browder et al Cancer Res 2000;60:1878). Methods: We conducted a phase II study of continuous low-dose etoposide (VP-16), alternating with cyclophosphamide (CP), in combination with thalidomide (T) and celecoxib (C) in adult patients with recurrent malignant gliomas. There was no limit on the number of prior therapies. Patients received VP-16 [35 mg/m2 (maximum 100 mg) daily for 21 days] alternating with CP [2 mg/kg (maximum 100 mg/day) for 21 days]. Thalidomide was started at 200 mg daily and increased by 100 mg weekly to a maximum of 1200 mg/day, as tolerated. Celecoxib was started at 200 mg twice daily and increased to 400 mg twice daily. MRIs were performed every 6 weeks. Patients were treated until tumor progression or development of unacceptable toxicity. Serum was collected for measurement of angiogenic peptides. Results: 48 patients were enrolled (15 female, 33 male). 28 had glioblastomas (GBM); 20 had anaplastic gliomas (AG). Median age was 53 years (range 33–74); median KPS was 70 (range 60–100). Patients had average of 2.1 prior chemotherapies; 33% had 3 or more prior chemotherapies. Toxicities included neutropenia (8 G3, 8 G4), leukopenia (13 G3, 8 G4), lymphopenia (26 G3), anemia (1 G3), thrombocytopenia (1 G3); nausea (1 G3), vomiting (3 G3), constipation (5 G3; 2 G4), colitis (2 G4), rash (1 G3), dizziness (1 G3); hypoxia (1 G3), and infection (2 G3). 2 patients had DVT and 6 had pulmonary emboli. There were no treatment related deaths. Fatigue was common but usually mild. 12% of patients had PR, 59% had SD, 29% progressed at their first scan. For GBM patients, median progression-free survival (PFS) was 11 weeks, 6 month-PFS was 9% and median survival was 21 weeks. For AG patients, median PFS was 14 weeks; 6 month-PFS was 26% and median survival was 41.5 weeks. Correlation of angiogenic peptide levels and response will be reported. Conclusions: Although there were some responders this regimen did not significantly improve survival in this heavily pretreated group of patients. However, further studies combining metronomic chemotherapy with more potent angiogenesis inhibitors such as lenalidomide or VEGFR inhibitors may be warranted. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document