Multi-parametric MRI guided dose escalated radiotherapy for treatment of localized prostate cancer (PCa): Initial toxicity results of a prospective phase II trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 25-25 ◽  
Author(s):  
Philip Blumenfeld ◽  
Mudit Chowdhary ◽  
Leslie A. Deane ◽  
Nick Pfanzelter ◽  
Stephanie Shors ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
High Dose ◽  
Volumetric Arc Therapy ◽  
Early Results ◽  
Gu Toxicity ◽  
Prospective Phase ◽  
Grade 3

25 Background: Multi-parametric MRI (mpMRI) of PCa uses advanced sequences to detect aggressive, high grade and bulky lesions. Given known advantages of hypofractionated radiotherapy (RT) to treat PCa (low a/b ratio), we conducted a phase II trial to escalate a high dose to mpMRI lesion(s) via Image-Guided (IG)-RT/Volumetric Arc Therapy (VMAT)/Stereotactic Body Radiotherapy (SBRT) technology. We present the acute toxicity results of this novel approach. Methods: 22 pts with mpMRI lesion(s) were prospectively treated to a course of IGRT/VMAT to the prostate & seminal vesicle +/- pelvic lymph nodes (PLN) to a dose of 45 Gy in 25 fractions followed by SBRT boost, 18 Gy in 3 fraction to the prostate with a simultaneous integrated boost 21 Gy in 3 fractions (EQD2 = 85.2 Gy using a/b 3 or 93.4 Gy using a/b 1.5) to the mpMRI prostatic lesion(s). Placement of 3 polymer based fiducial markers visible in both CT and MRI for image co-registration and treatment guidance was performed. Genitourinary (GU) and gastrointestinal (GI) adverse events (AE) were scored using CTCAE v4. DSMC approved reporting of acute AE results prior to completion of trial accrual as an interim safety assessment prior to final trial accrual. Results: Median age was 66.5 years (range: 57-80). All patients had PI-RADS grade 3-5 mpMRI lesion(s); 41.0%, 45.4% and 13.6% having 1, 2 and 3 lesions respectively. Ten (45%) pts had Gleason Score (GS) 8-10 and 12 had GS 7 disease. Median PSA was 8.97 (range: 4.0-77.9). Eleven (50%), 10 (46%), and 1 (5%) pts had stage T1, T2, and T3 tumor, respectively. Nine pts received treatment to the PLN and 15 received androgen deprivation therapy. All patients completed the protocol treatment without reporting acute GI or GU AEs grade ≥3 during treatment or at follow up. Grade 2 GI (diarrhea) and GU toxicity (frequency) was seen in 2 (9%) and 9 (41%) pts, respectively, during treatment. Of the 16 pts (71%) with least 3 months follow-up all grade 2 GI and 55.5% GU toxicities had resolved. Conclusions: Early results of this prospective Phase II study suggest that high-dose RT for localized PCa via mpMRI-guided RT/VMAT and SBRT boost is tolerable with a favorable acute toxicity profile.

Phase II trial of high-dose interleukin-2 (IL-2) and stereotactic radiation therapy (SABR) for metastatic clear cell renal cell carcinoma (ccRCC): Interim analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 532-532 ◽  
Author(s):  
Raquibul Hannan ◽  
Dan Ishihara ◽  
Kristi Louder ◽  
Chul Ahn ◽  
Vitaly Margulis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Trial ◽  
Interleukin 2 ◽  
Outcome Analysis ◽  
High Dose ◽  
Cell Renal Cell Carcinoma ◽  
Number Of Patients ◽  
Grade 3

532 Background: We report a planned interim analysis of a single-arm, open-label, phase II trial of HD IL-2 and SABR in multiple ccRCC metastatic sites. Methods: Metastatic ccRCC patients eligible for IL-2 were enrolled and received SABR of 1 or 3 fractions (fx) to up to 6 sites. IL-2 (Proleukin) was administered within 84 hours from the last SABR fx at 600,000 IU/kg every 8h for up to 14 doses in a monitored setting followed by another week after a week break. Eligible (responding) patients received a second course in > 12 weeks. The primary endpoint is the response rate (RR) as evaluated by iRECIST. The study is powered to detect a 60% improvement compared to the historically reported 23% RR for IL-2. Results: 16 patients were enrolled between August 2013 and July 2015; two were withdrawn from the study due to cardiac events prior to receiving IL-2 infusions. The median follow up was 9 months. A median of 2 (1-3) sites were treated with SABR with a median dose of 24.5 Gy (21-27 Gy) for single fx and 30Gy for 3 fx (25-33 Gy). All patients received the first week of IL-2 with a median of 10.5/14 doses; 64% received the second week (9/14) with a median of 7/14 doses. Two patients refused a second week of IL-2 and one was unable to receive it due to thyrotoxicosis. PICC line DVT delayed the second week of IL-2 in two patients. 29% of patients (4/14) received a second course of IL-2. The rate of grade 3 toxicity was 64% with no > grade 3 toxicity. The overall toxicities were expected of IL-2 treatment, transient and resolved after treatment discontinuation. In two cases, grade 1 toxicity was attributed to SABR. At this interim, ten patients underwent at least two follow up scans and were evaluable for outcome analysis. The RR was 40%, with one patient presenting complete response and 3 patients showing partial response. The median duration of overall response was 5 months, with a median stable disease duration of 6 months. Local control rate for SABR-treated lesions was 95%. Conclusions: The addition of SABR to IL-2 increased the RR in mRCC patients of about 2-folds compared to IL-2 alone, despite the reduced number of patients receiving the second week of IL-2. No significant increase in toxicity was observed. Clinical trial information: NCT01896271.

A Prospective Phase II Comparison of Stem Cell Source Using Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) RE—Induction, Then High Dose Fludarabine, Busulfan (FLUBU) and Autologous (ASCT) or Allogeneic (AlloSCT) Hematopoietic Blood Stem Cell Transplantation for Mantle Cell (MCL) and Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 915-915
Author(s):  
Douglas A. Stewart ◽  
Michael Voralia ◽  
Ahsan Chaudhry ◽  
Oluyemi Jeje ◽  
Donald Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Phase Ii ◽  
Blood Stem Cell ◽  
High Dose ◽  
Free Survival ◽  
Stem Cell Source ◽  
Cell Source ◽  
Prospective Phase ◽  
Grade 3

Abstract Introduction: A “genetically-randomized” prospective phase II study was designed to compare stem cell source following novel, uniform, and expected low toxicity re-induction and high dose chemotherapy for indolent B-cell NHL. Patients and Methods: Pts with MCL in 1st remission or 1st relapse, or other indolent B-cell lymphoma in 1st or 2nd relapse were eligible providing adequate organ function and age <65 years. Pts received RICE (Rituximab 375mg/m2 d1,8,15,22, Ifosfamide 1.67g/m2 d16-18, Carboplatin AUC=5 d17, Etoposide 100mg/m2 d16-18), with G-CSF d22-30, and apheresis d29-31 if ASCT, then FluBu (Fludarabine 50mg/m² d-6to-2, Busulfan 3.2 mg/kg IV daily d-5to-2) and SCT d0. GVHD prophylaxis for AlloSCT involved ATG 4.5mg/kg, MTX and CSA. Results: The initial 43 pts accrued from 06/2001-03/2004 included Follicular=30, MCL=7, SLL=4, other histology=2. Disease status was 1st remission=2, 1st relapse=18, 2nd relapse=12, 10 refractory=11. The median EFS following most recent prior chemotherapy was 7 mos. RICE resulted in an overall RR of 72%. Blood stem cell source was ASCT=27, donor SCT=16 (related=14, unrelated=1, syngeneic=1). For ASCT, a median of 5.9 (1–14.5) x106 CD34+ cells/kg were collected from 1 (n=17) or 2 (n=10) 15-25L aphereses. Three pts required a second mobilization procedure. 16/24 pts converted from positive to negative marrow biopsies post-RICE. Two pts had NHL detected in the autograft. FluBu resulted in no acute Bearman grade 3-4 RRT(overall 100d non-relapse mortality (NRM)=0% for both ASCT and donor SCT). Median engraftment times were slightly longer post AlloSCT than ASCT (ANC>0.5 = 15 vs 11d, and platelets>20 = 12 vs 9d, respectively). Of 15 AlloSCT pts, grade 3–4 aGVHD occurred in 5 (33%), cGVHD occurred in 64%, and death from extensive cGVHD + infection occurred in 5 pts from 7-13mo post-AlloSCT (overall NRM=33% for AlloSCT). With a median follow-up of 22mo, the 2 year projected outcome of ASCT vs Allo/Syngeneic-SCT for relapse-free survival (RFS) was 64% vs 87% (logrank p=0.48), event-free survival (EFS) 63% vs 52% (logrank p=0.38), and overall survival (OS) 86% vs 46% (logrank p=0.0018), respectively. For relapsed follicular lymphoma only, the 2yr EFS was 61% vs 59% (logrank p=0.49) and OS 100% vs 51% (logrank p=0.0009) for ASCT (n=19) vs Allo/Syngeneic SCT (n=11), respectively. Conclusion: These preliminary results suggest that RICE can "in-vivo" purge autografts but mobilizes blood stem cells only moderately well. RICE-FluBu/ASCT may result in prolonged EFS with significantly less NRM than AlloSCT.

High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Primary CNS Lymphoma: Updated Results from a Pilot and Phase II Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pilot Trial ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Abstract Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). A 5-year overall survival probability (OS) of 69% could be demonstrated in 30 pts within a phase-II trial on HDT and ASCT with consolidating whole-brain-irradiation (WBRT) (Illerhaus et al. JCO 2006). A subsequent pilot trial on HDT and ASCT without WBRT showed a 5-year OS of 77% (Illerhaus et al. Haematologica 2008). Here we give an update of our two different treatment regimens and future perspectives. Patients and Methods: Thirty pts. ≤65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 3 cycles of high-dose methotrexate (MTX, 8 g/m2), 1 cycle of AraC (2× 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization. Conditioning regimen included BCNU (400 mg/m2) and TT (2×5 mg/kgBW) followed by ASCT. Hyperfractionated WBRT (45 Gy, 2×1Gy/d) was administered as consolidation. In our subsequent pilot trial 13 pts. (age 38–67 years) were treated without consolidating WBRT; CHT was intensified with 4 cycles MTX 8g/m2, 2 cycles AraC (2× 3 g/m2) and TT (40 mg/m2). Dose escalated HDT included BCNU (400 mg/m2) and TT (4×5 mg/kgBW) followed by ASCT. WBRT was reserved for pts. not responding to CHT. Results: Median follow-up of the 30 pts. treated within our phase II trial was extended to 95 months (mo), the updated 5-year OS of all pts. is 66.6% and 82,3% of the subgroup of pts. who underwent HDT and ASCT (n=23), respectively. Three additional deaths occurred due to relapse (n=2) after 45 and 71 mo and due to comorbidity (n=1) after 103 mo. Five of 30 pts. developed severe leukoencephalopathy during follow-up. With a median follow-up of 35 mo in the 13 pts. treated within the pilot-phase without consolidating WBRT 3-year OS of all pts. is 77%. No further relapse or non-relapse mortality occurred in this pilot-group during. Most recent follow-up data will be presented in detail. Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as initial therapy for pts. with PCNSL. The restriction of WBRT to refractory disease shows similar OS rates and a decrease in neurotoxicity. In an ongoing multicenter phase-II trial immunotherapy with rituximab is combined with HDT and ASCT to further increase remission rates. A future randomized trial should be focused on the efficacy of consolidation with HDT supported by ASCT.

Combination Biologic Therapy as Initial Treatment for Follicular Lymphoma: Initial Results From CALGB 50701 - a Phase II Trial of Extended Induction Epratuzumab (anti-CD22) and Rituximab (anti-CD20)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 427-427 ◽  
Author(s):  
Barbara Grant ◽  
John P. Leonard ◽  
Jeffrey L Johnson ◽  
Lale Kostakoglu ◽  
Eric Hsi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Good Tolerability ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 427 Rituximab is effective as single agent therapy in the treatment of follicular lymphoma (FL), and when combined with chemotherapy has extended remissions and survival. Epratuzumab (Immunomedics), a humanized anti-CD22 monoclonal antibody, also has single agent activity in FL, and in combination with rituximab led to durable complete responses in the treatment of patients (pts) with relapsed and refractory indolent NHL. To evaluate the hypothesis that combining a second biological agent with rituximab might improve efficacy with good tolerability, the CALGB treated 60 previously untreated pts with epratuzumab and rituximab in a multicenter phase II trial and we report here the preliminary response and toxicity findings. Rituximab was administered at 375 mg/m2 iv weekly for four weeks, then every 8 weeks for four additional doses for a total of 8 doses over 9 months. Epratuzumab, was given at 360 mg/m2 two days before the first rituximab dose to assess toxicity. From week 2 on, epratuzumab was given before the rituximab on the same day for a total of 8 doses over 9 months. Fifty-seven evaluable pts were enrolled between May 2008 and September 2009. FLIPI scores at study entry were 13 (22%) low; 28 (47.5%) intermediate; and 18 (30.5%) high. Fifty-three pts completed all therapy through month 9. One pt was taken off therapy due to progression after month 5. One pt died during induction from line sepsis. Two pts were taken off study due to adverse events, 1 during induction (grade 4 thrombosis and MI), 1 following month 5 (dyspnea, hypoxia and pulmonary NOS). All other toxicities were grade 3 or lower, including fatigue (grade 3 3%, grade 2 17%), nodal pain (grade 3 5%, grade 2 8%), and cytokine release and pruritis (grade 2, 5% each). To date, there have been 19 CRs (33.3%), 29 PRs (50.9%)(ORR 84.2%); 9 (15.8%) had stable disease. All 19 CR patients completed all treatment. The mean time to CR was 9 months. Two patients progressed after a period of stable disease, and 25 of the 29 patients who achieved PR remain in response. All 19 CRs also remain in remission at this point with a median follow-up of 0.82 years (range 0.52 to 2.0). FLIPI score was not predictive of response. The CR rate in low risk pts was 31%, 44% in intermediate risk and 18% in high risk pts. There was a trend toward higher CR rate among patients with FcgR2A His (n=10, CR 60%) and to a lower CR rate among those with FcgR2A Arg (n=14, CR 14.3%). Correlations with PET scan at week 3, with tissue biomarkers and to statin use are being analyzed. Rituximab and epratuzumab is an effective and very well tolerated regimen with an ORR of 84% in previously untreated patients with follicular lymphoma. Disclosures: Off Label Use: Use of Epratuzumab, a humanized antiCD22 monoclonal antibody in treatment of follicular lymphoma. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Jones:Glaxo Smith-Kline: Consultancy; Abbott: Research Funding. Cheson:Genentech: Consultancy.

Prolonged Survival with Low Incidence of CNS Relapse and Late Toxicities in a Retrospective Series of 278 Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma Treated with Intensified Chemotherapy with or without Rituximab At Diagnosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1606-1606
Author(s):  
Annalisa Chiappella ◽  
Alessia Castellino ◽  
Maria Giuseppina Cabras ◽  
Anna Marina Liberati ◽  
Andrea Evangelista ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Secondary Malignancies ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Dose Dense

Abstract Abstract 1606 Introduction. Diffuse Large B-cell Lymphoma (DLBCL) patients at high-risk (age-adjusted International Prognostic Index (aa-IPI) 2–3), had a dismal prognosis if treated with conventional chemotherapy. The introduction of intensive regimens and the addition of monoclonal antibody anti-CD20, improved prognosis, but some issues remain unresolved such as: the risk of central nervous system (CNS) relapses and the incidence of late toxicities. We analyzed a series of young DLBCL patients at high-risk consecutively treated in four prospective trials by the Italian Lymphoma Foundation (FIL) with the aim to assess the risk of CNS relapses and late toxicities in this series of patients with a prolonged follow-up Methods. From 1986 to 2006, 278 patients with DLBCL with aa-IPI 2–3 at diagnosis, were enrolled in four consecutive trials previously reported. Thirty-two into a phase II study, treated with 12 weekly infusion of MACOP-B; 39 into a phase II trial with eight weekly MACOP-B infusions followed by high-dose cytarabine, mitoxantrone and dexamethasone (MAD) plus standard BEAM and autologous stem cell transplantation (ASCT); 95 in a phase III trial that randomized high-dose sequential (HDS) chemotherapy plus ASCT (45 patients) vs six courses of dose-dense intensified CHOP (iCHOP) (50 patients); 112 into a phase II trial with four courses of iCHOP in combination with Rituximab followed by Rituximab-MAD + BEAM and ASCT. CNS prophylaxis was not mandatory in the four protocols. Updated data regarding of survival, CNS relapses and late toxicities were recorded on June 2011. Results. Clinical characteristics were: aa-IPI 2 in 55%, aa-IPI 3 in 45%, PS > 2 in 66%, LDH upper normal value in 89%, number of extranodal sites > 2 in 35%, bone marrow involvement in 27% of patients, with no statistical differences between the four trials. With a median follow-up of five years, 5-year Overall Survival (OS) was 63% (95% CI: 57–69%) in the whole series; 5-year OS by treatment was 41% (95%CI: 24–74%) in MACOPB, 54% (95%CI: 37–68%) in MACOPB+MAD+BEAM and ASCT; 53% (95%CI: 38–67%) in HDS+ASCT; 58% (95%CI: 43–70%) in iCHOP; 79% (95%CI: 70–86%) in R-iCHOP+R-MAD+BEAM and ASCT. In a multivariate analysis, the risk of death was significantly reduced in R-iCHOP+R-MAD+BEAM and ASCT (p<.001) and was adversely influenced by age with a progressive increase of five years at diagnosis (p.008) or aa-IPI3 (p.001). Four patients experienced CNS relapses, three of them in R-iCHOP+R-MAD+BEAM and ASCT and one in MACOPB. Only one of the four patients received CNS prophylaxis with intrathecal Methotrexate, even if all of them were at risk for CNS relapse according to Italian Society of Hematology guidelines (Barosi, Hematol 2006). Cumulative incidence of CNS recurrence at 10 years for R-iCHOP+R-MAD+BEAM and ASCT regimen was 3.6% (0 to 7.8). Most frequent late toxicities were dyslipidemia and secondary amenorrhea. Regarding to secondary malignancies, myelodisplasia or acute myeloid leukemia were recorded in three patients, two of them treated with R-iCHOP+R-MAD+BEAM and ASCT, at a median time of seven years off therapy. The actuarial risk of secondary malignancies at 10 years for R-iCHOP+R-MAD+BEAM and ASCT was 4.2% (0 to 10). Conclusions. The addition of Rituximab to dose-dense iCHOP plus high-dose chemotherapy plus BEAM and ASCT improved the outcome in young untreated DLBCL patients at poor prognosis, with an acceptable risk of secondary malignancies and late toxicities. A careful identification of patients at risk could avoid the risk of CNS relapse. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

Weekly bortezomib in the treatment of patients (pts) with previously treated multiple myeloma: A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7547-7547 ◽  
Author(s):  
F. A. Greco ◽  
D. R. Spigel ◽  
J. H. Barton ◽  
C. Farley ◽  
M. T. Schreeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Research Network ◽  
High Dose ◽  
Weekly Schedule ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Previously Treated ◽  
Grade 3

7547 Background: Bortezomib, administered on a twice-weekly schedule, is now a standard part of treatment for patients with multiple myeloma. Weekly bortezomib schedules have shown activity in other cancer types, and are more convenient than twice weekly schedules. In this multicenter, community-based phase II trial, we evaluate the feasibility, toxicity, and efficacy of weekly bortezomib in pts with previously treated multiple myeloma. Methods: Eligibility criteria included a diagnosis of multiple myeloma treated with 1 or 2 previous systemic regimens (only 1 if first-line therapy included high-dose therapy); ECOG PS 0–2; creatinine < 2.0 mg/dL; WBC ≥ 3000/μL; ANC > 1000/μL; platelets ≥ 50,000/μL; no peripheral neuropathy > grade 1; informed consent. All pts received bortezomib 1.6mg/m2 IV on days 1, 8, 15, and 22 of each 5-week cycle. Pts were reevaluated at 10-week intervals; treatment continued for 8 cycles (40 weeks) or until myeloma progression. Results: Between 5/04 and 12/05, 37 pts entered this trial. Pt characteristics: median age 70 years; male/female, 20/17; 24 pts (65%) had received 2 previous regimens (previous high dose therapy, 2 pts); elevated β-2 microglobulin, 27 pts (73%). Of 26 pts evaluated, 13 pts (50%) had major responses, 11 pts (42%) stable disease, and 2 pts (8%) had progression. After a median follow-up of 7 months, projected median PFS is 9.6 months; overall survival at 1 year is 81%. Weekly bortezomib was well tolerated by most pts. Grade 3/4 toxicities included fatigue (21%), diarrhea (11%), neutropenia (7%), thrombocytopenia (4%), all others < 5%. No grade 3/4 neuropathy occurred. Only 1 pt required bortezomib dose reduction during treatment, and 2 pts discontinued treatment because of toxicity (myelosuppression, 1; fatigue/dehydration, 1). Conclusions: Weekly bortezomib is a convenient, well tolerated treatment for pts with previously treated multiple myeloma. Overall response rates with this schedule are similar to those previously reported with the standard twice-weekly schedule. Further followup is necessary to better evaluate the duration of response and the incidence of cumulative toxicities. [Table: see text]

A phase II trial of temozolomide and vinorelbine for patients with recurrent brain metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2050-2050
Author(s):  
F. M. Iwamoto ◽  
A. M. Omuro ◽  
J. J. Raizer ◽  
C. P. Nolan ◽  
A. Hormigo ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Minor Response ◽  
Radiographic Response ◽  
Whole Brain Radiation ◽  
Heavily Pretreated ◽  
Grade 3

2050 Background: Temozolomide has shown modest efficacy in the treatment of recurrent brain metastases. We designed a regimen combining temozolomide with vinorelbine, a lipophilic agent that crosses the blood-brain barrier, trying to improve efficacy. Methods: This is a phase II trial with 28-day cycles using temozolomide (150 mg/m2, days 1–7 and 15–21) and vinorelbine on days 1 and 8. We previously reported a phase I trial that established an MTD of 30 mg/m2 of vinorelbine in this combination, but the dose was decreased to 25 mg/m2 in this phase II trial. The phase II component was planned as a two-stage clinical trial. Since two or more responses were observed after the 20 initial patients, 15 more assessable patients were required. This design had a 91% probability to detect a true response rate of 20% or more. The primary endpoint was objective radiographic response. Secondary endpoints include OS, PFS and toxicity. Patients = 18 years old with KPS = 60, adequate organ function and progressive or recurrent brain metastases were eligible. Results: Thirty-six patients (13 men, 23 women) with a median age of 56 years (range, 38–76) and median KPS of 80 were enrolled. The primary tumor sites were lung (n=19), breast (n=11), colon (n=2), bladder (n=1), endometrium (n=1), head/neck (n=1) and kidney (n=1). Prior therapies included whole-brain radiation therapy (81%), chemotherapy (97%), radiosurgery (42%) and brain metastasis resection (47%). Objective radiographic response was 7% (1 CR and 1 minor response); 4 patients had SD and 23 PD. Three patients withdrew consent and did not undergo follow-up scans, 2 patients did not receive the planned treatment and 2 patients recently began treatment and have not been assessed. The median follow-up was 12.3 weeks and 72% of patients have died. Median PFS and OS were 8.3 weeks and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and 3 patients were removed from the study due to myelosuppression. Conclusions: In this heavily pretreated population of patients with brain metastases, adding vinorelbine to temozolomide does not seem to improve response rates as compared to temozolomide alone. Single-agent temozolomide also has a more favorable toxicity profile. [Table: see text]

Early toxicity in a prospective phase I/II trial of MRI-assisted focal boost integrated with HDR monotherapy for low- and intermediate-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 120-120
Author(s):  
Laura D'alimonte ◽  
Joelle Antoine Helou ◽  
Gerard Morton ◽  
Hans T. Chung ◽  
Merrylee McGuffin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
High Dose Rate ◽  
High Dose ◽  
Intermediate Risk ◽  
Hdr Brachytherapy ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Prospective Phase

120 Background: There is growing evidence for the use of High Dose Rate (HDR) brachytherapy as monotherapy for the treatment of low and intermediate risk prostate cancer patients. With the increasing availability of magnetic resonance imaging (MRI) there is an opportunity to further escalate dose to the dominant intraprostatic lesion (DIL). We report acute toxicity of this prospective phase I/II trial. Methods: Eligible patients had low- and intermediate risk prostate cancer, IPSS < 16, were medically eligible for HDR brachytherapy treatment and had an identified DIL on multiparametric MRI (mpMRI) prior to brachytherapy treatment. Patients were treated with 19 Gy delivered in one fraction to the whole prostate. A 0-5mm expansion was applied to the DIL to define the PTV DIL, with a DIL PTV D90 to receive > 23Gy based on previous experience. Toxicity was assessed using CTCAE v.4.0 at baseline, 6 weeks 3, 6, 9 and 12 months post brachytherapy. Results: A total of 34 patients have undergone HDR monotherapy treatment with an integrated DIL boost with a median follow up of 6 months. The median age was 67 years (range 46-80). At presentation, median PSA was 6.1 ng/mL (range 2.5-16.4). Three, 26, and 6 patients had low, low intermediate and high intermediate risk disease. Baseline characteristics were PIRAD 5 (n = 21) and PIRAD 4 (n = 13), median prostate volume was 38 cc (range 18-54). The median DIL volume was 2.8 cc (range 1.14-7.8). The median DIL D90 was 27 Gy (range 19-35.8). No patients experienced acute or late grade 2+ GI toxicity. The percentage of acute grade 2 GU toxicity were as follows; retention 62%, frequency 18%, urinary tract pain 6%. One patient had acute clot retention requiring catheterization x1 day and has been catheter-free since. Late grade 2 GU toxicity (alpha blockers) was reported in 6/16 patients at 6 months. Conclusions: The use of mpMRI to define and further escalate dose to the DIL using HDR monotherapy is feasible with minimal acute toxicities. Further long term follow up is required to determine the efficacy of treatment, and impact on quality of life and late toxicities. Clinical trial information: NCT02623933.

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