Phase I and Pharmacokinetic Study of E7070, a Novel Chloroindolyl Sulfonamide Cell-Cycle Inhibitor, Administered as a One-Hour Infusion Every Three Weeks in Patients With Advanced Cancer

2002 ◽  
Vol 20 (16) ◽  
pp. 3508-3521 ◽  
Author(s):  
E. Raymond ◽  
W.W. ten Bokkel Huinink ◽  
J. Taïeb ◽  
J.H. Beijnen ◽  
S. Faivre ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Maximum Tolerated Dose ◽  
Tumor Burden ◽  
Eligibility Criteria ◽  
Time Curve ◽  
Cell Cycle Inhibitor ◽  
Pretreated Group ◽  
Heavily Pretreated ◽  
Group A ◽  
Group B

PURPOSE: The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor. PATIENTS AND METHODS: E7070 was given as a 1-hour intravenous infusion every 3 weeks in two groups of patients with advanced solid tumors who met prespecified eligibility criteria (group A) or who met the same eligibility criteria but in addition were less heavily pretreated and had more favorable liver functions (group B). RESULTS: Forty patients (31 patients in group A and nine patients in group B) were entered. Dose escalation proceeded through eight levels (range, 50 to 1,000 mg/m2). In group A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring during the first cycle in two of seven patients treated at the doses of 700 mg/m2 and two of four patients treated at 800 mg/m2. Identical dose-limiting toxicities were observed in zero of six and two of three patients from group B at doses of 800 and 1,000 mg/m2, respectively. Other toxicities included acne-like skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses greater than 400 mg/m2, the area under the concentration-time curve increased disproportionately to the administered dose. Tumor stabilization lasting ≥ 6 months was observed in six assessable patients. CONCLUSION: The recommended doses of E7070 in this schedule were 700 mg/m2 (group A) and 800 mg/m2 in patients who were less heavily pretreated (group B) with a moderate tumor burden. Prolonged disease stabilization observed in this study might warrant further investigation of E7070 in selected tumor types.

Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma

2008 ◽  
Vol 26 (36) ◽  
pp. 5950-5956 ◽  
Author(s):  
Jeffrey S. Weber ◽  
Steven O’Day ◽  
Walter Urba ◽  
John Powderly ◽  
Geoff Nichol ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Complete Response ◽  
Pharmacokinetic Profile ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Clinical Activity ◽  
Multiple Doses ◽  
Group A ◽  
Group B

PurposeThe primary objective of this phase I/II study was to determine the safety and pharmacokinetic profile of either transfectoma- or a hybridoma-derived ipilimumab. Secondary objectives included determination of a maximum-tolerated dose and assessment of clinical activity.Patients and MethodsEighty-eight patients with unresectable stage III or IV melanoma with at least one measurable lesion were treated. Mean age was 59 years, with 65% male and 35% female patients, and 79% of patients had received prior systemic therapy. Single doses of ipilimumab up to 20 mg/kg (group A, single dose), multiple doses up to 5 mg/kg (group A, multiple dose), and multiple doses up to 10 mg/kg (group B) were administered.ResultsSingle dosing up to 20 mg/kg of transfectoma antibody was well tolerated, as were multiple doses up to 10 mg/kg without a maximum-tolerated dose. In group B, dose-limiting toxicity was seen in six of 23 melanoma patients. Grade 3 or 4 immune-related adverse events (irAEs) were observed in 14% of patients (12 of 88 patients), and grade 1 or 2 irAEs were seen in an additional 58%. The half-life of ipilimumab was 359 hours. In group B, there was one partial response (23+ months), one complete response (21+ months), and seven patients with stable disease (SD), for a disease control rate of 39%. Two patients in group B with SD had slow, steady decline in tumor burden that was ongoing at 1 year of observation.ConclusionIpilimumab has activity in patients with metastatic melanoma. Late responses were observed in patients with prolonged SD.

Advances in the approach to treatment of bilateral retinoblastoma: 26-year experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22009-e22009 ◽  
Author(s):  
Rejin Kebudi ◽  
Samuray Tuncer ◽  
Sema Bay Buyukkapu ◽  
Serra Sencer ◽  
Omer Gorgun ◽  
...  
Keyword(s):  
Survival Rate ◽  
Late Effects ◽  
Treatment Decision ◽  
Tumor Burden ◽  
Treatment Modalities ◽  
Second Cancer ◽  
Bilateral Retinoblastoma ◽  
Group A ◽  
Contralateral Eye ◽  
Group B

e22009 Background: Bilateral retinoblastomas (BRBS) comprise 25 % of all RBS. Treatment decision depends on tumor burden, potential for vision, status of the contralateral eye. As the survival rate in retinoblastoma has increased, ocular salvage and late effects has become an important issue. The aim of the study is to evaluate the demographic features, treatment modalities, and late effects in BRBS. Methods: BRBS treated in Istanbul University, Oncology Institute and Opthalmology Department between 1990-2016 were retrospectively evaluated. All patients were multidisciplinarily evaluated for chemotherapy (chemoreduction /adjuvant), local opthalmologic therapies (transpupillary thermotherapy, cryotherapy, plaque), radiotherapy, enucleation. The chemotherapy (CT) protocol used had vincristine, cisplatin, etoposide, cyclophosphamide until 2009, and vincristine, etoposide, carboplatin since then. Since 2011, intraarterial, intravitreal CT was also used. Results: 114 BRBS (228 eyes) (56 male, 58 female) with a median age of 9 months (20days-42 mo.) were evaluated. Three had extraocular disease, two trilateral RBS. Seventeen had history of retinoblastoma in their families. According to ICRB classification, there were 67 eyes in group E, 43 group D, 27 group C, 45 group B, and 19 group A. Enucleation was done in 68 (30%) eyes, mostly group E. During 1990-2000, 23/26 patients underwent enucleation, whereas 45/88 underwent enucleation after 2000. Radiotherapy was used for 30 eyes, most before 2000. Bone and soft tissue deformities and cataracts were observed in irradiated patients. Five patients had a second cancer (4 sarcomas, 1 meningioma) at a median of 11 years, four in irradiated sites. The 5 yr survival was 93.5%, 9 patients died, 4 due to second cancer. Conclusions: As the survival rate in intraocular BRBS has increased, ocular salvage and late effects have gained importance. Chemoreduction (systemic, intraarterial) and local ophtalmic therapies enable preservation of vision in most group A, B, C tumors and some D tumors. Most group E tumors require enucleation. Radiotherapy is not used in most RBS in the last decade. Intra-arterial chemotherapy is promising in maintaining ocular salvage.

DNA cytometric parameters as prognostic factors of chemoimmunotherapy for ovarian cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17041-e17041
Author(s):  
Galina Andreevna Nerodo ◽  
Oleg Ivanovich Kit ◽  
Inna Arnoldovna Novikova ◽  
Anna Ardzha ◽  
Ekaterina V. Verenikina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Tumor Cells ◽  
Intraperitoneal Administration ◽  
Proliferation Index ◽  
Becton Dickinson ◽  
Dna Index ◽  
Group A ◽  
Group B

e17041 Background: The aim of the study was to analyze chemoimmunotherapy influence on DNA cytometric parameters in patients with ovarian cancer. Methods: The study included stage IIIC-IV ovarian cancer patients divided into two groups in dependence on the treatment: group A – 21 patients who did not receive neoadjuvant chemotherapy before surgery; group B – 24 patients who received neoadjuvant chemoimmunotherapy with intraperitoneal administration of interferon-gamma (ingaron) and the following surgery. The groups were identical in terms of the disease stages, age and general condition of patients. DNAs were analyzed in fresh tumor tissues using CycleTEST Plus DNA Reagent Kit (Becton Dickinson, USA). The data were processed using the ModFit LT program allowing analysis of ploidy and distribution of tumor cells in phases of the cell cycle. The proportion of cells with different DNA content in the histogram was calculated as a percentage of the total number of studied cells. Proliferation index (PI) was calculated as the total amount of tumor cells in S and G2+М phases of the cell cycle. Results: Full-volume surgery (panhysterectomy+omentectomy) was performed in 52.4% in group A and in 92% in group B, adnexectomy only – in 38.1% and 8%, respectively; exploratory surgeries were performed in group A only – 9.5%. During 2 years of the observation, recurrence in group A was found in 38% of patients, in group B – in 12.5%. Analysis of DNA cytometric parameters showed the minimal proliferation rates (percentage of cells in S phase) in group B – 12.6±2.3%, compared with 20.7±3.4% in group A. PI was lowest in group B – 13±2.7%, compared with group A – 22.4±3.3% (p≤0.05). Significant decrease in the DNA index by 1.3 times was noted in patients in group B in comparison with group A (1.11±0.01% and 1.4±0.05%, respectively) (p≤ 0.05). Conclusions: Thus,DNA cytometric parameters reflect the effectiveness of chemoimmunotherapy and can be used as prognostic factors.

scholarly journals Effect of Coadministered Fat on the Tolerability, Safety, and Pharmacokinetic Properties of Dihydroartemisinin-Piperaquine in Papua New Guinean Children with Uncomplicated Malaria

2014 ◽  
Vol 58 (10) ◽  
pp. 5784-5794 ◽  
Author(s):  
B. R. Moore ◽  
J. M. Benjamin ◽  
S. Salman ◽  
S. Griffin ◽  
E. Ginny ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Clinical Laboratory ◽  
Parasite Clearance ◽  
Population Based ◽  
Laboratory Assessment ◽  
Time Curve ◽  
Group A ◽  
Group B ◽  
Papua New Guinean

ABSTRACTCoadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age group. The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5-mg-base/kg doses were given with water (n= 14, group A) or milk (n= 16, group B), with regular clinical/laboratory assessment and blood sampling over 42 days. Plasma PQ was assayed by high-performance liquid chromatography with UV detection, and DHA was assayed using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models for PQ and DHA were developed using a population-based approach. DHA-PQ was generally well tolerated, and initial fever and parasite clearance were prompt. There were no differences in the areas under the concentration-time curve (AUC0–∞) for PQ (median, 41,906 versus 36,752 μg · h/liter in groups A and B, respectively;P= 0.24) or DHA (4,047 versus 4,190 μg · h/liter;P= 0.67). There were also no significant between-group differences in prolongation of the corrected electrocardiographic QT interval (QTc) initially during follow-up, but the QTctended to be higher in group B children at 24 h (mean ± standard deviation [SD], 15 ± 10 versus 6 ± 15 ms0.5in group A,P= 0.067) and 168 h (10 ± 18 versus 1 ± 23 ms0.5,P= 0.24) when plasma PQ concentrations were relatively low. A small amount of fat does not change the bioavailability of DHA-PQ in children, but a delayed persistent effect on ventricular repolarization cannot be excluded.

scholarly journals Pharmacokinetics of Oritavancin in Plasma and Skin Blister Fluid following Administration of a 200-Milligram Dose for 3 Days or a Single 800-Milligram Dose

2005 ◽  
Vol 49 (1) ◽  
pp. 148-152 ◽  
Author(s):  
Gerald J. Fetterly ◽  
Christine M. Ong ◽  
Sujata M. Bhavnani ◽  
Jeffrey S. Loutit ◽  
Steven B. Porter ◽  
...  
Keyword(s):  
Dose Group ◽  
Fluid Model ◽  
Study Drug ◽  
Pharmacokinetic Analysis ◽  
Blister Fluid ◽  
Time Curve ◽  
Drug Concentrations ◽  
Complicated Skin ◽  
Group A ◽  
Group B

ABSTRACT Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUCblister fluid/AUCplasma ratios) were evaluated using a t test (α = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUCblister fluid/AUCplasma ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 μg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.

Low Dose TBI Based Nonmyeloablative Conditionings for Allografting in Multiple Myeloma: Impact of Disease Status at Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2310-2310
Author(s):  
Luisa Giaccone ◽  
Marcello Rotta ◽  
Bernardino Allione ◽  
Fabrizio Carnevale-Schianca ◽  
Carlo Rosanelli ◽  
...  
Keyword(s):  
Complete Remission ◽  
Partial Response ◽  
Disease Progression ◽  
Stable Disease ◽  
Low Dose ◽  
Tumor Burden ◽  
P Value ◽  
Refractory Disease ◽  
Group A ◽  
Group B

Abstract The curative potential of allogeneic hematopoietic cell transplantation (HCT) with low dose total body irradiation (TBI) based conditionings relies exclusively upon a graft-versus-myeloma effect through donor lymphocytes. Thus, low tumor burden and well-controlled disease at transplant could play a pivotal role. Forty-four consecutive patients with myeloma were treated at 4 different Institutions. Thirty newly diagnosed patients (group A) received a planned autologous transplant with melphalan 200 mg/m2 followed by 200 cGy TBI and allogeneic G-CSF mobilized PBSC infusions from HLA identical siblings. Median time from diagnosis to HCT was 9 months (range, 5–46). At allografting, 7 (23%) patients were in complete remission (CR), 17 (57%) in partial response (PR) and 6 (20%) had refractory disease. The remaining 14 patients received fludarabine 90 mg/m2 and 200 cGy TBI followed by allogeneic PBSC from HLA identical siblings as salvage therapy (group B) after a median of at least 2 lines of previous chemotherapy (range, 2–5); all patients, except one, had received 2 autologous transplants. Patients in group B underwent allografting at a median of 37 months (range, 15–105) from diagnosis; 7 (50%) were in PR, 3 (21%) had refractory disease and 4 (28%) were in overt progression. Post-grafting immunosuppression consisted of cyclosporine and micophenolate mofetil in both groups. All patients readely engrafted with median donor T cell chimerism of 97% (range, 55–100%) at day 100. Overall, 64% (28/44) and 43% (19/44) patients developed acute graft-versus-host disease (GVHD) and chronic clinical extensive GVHD, respectively. There were no significant differences in engraftment kinetics and incidence of GVHD between the 2 groups. After a median follow-up of 16 months (range, 2–50) in group A and 19 months (range, 2–48) in group B, treatment related mortality was 23% among patients who received HCT earlier (group A) and 21% among those who were treated later (group B) in the disease course. Overall survival was 74% and 43% in group A and B, respectively. Disease responses are described in the table. n complete remission partial response stable disease progression Disease response Group A 30 17 6 7 0 Group B 14 0 0 3 11 p value – 0.0001 0.08 0.3 <0.0001 Among patients in group A, 4 relapsed after obtaining CR. Three of them received donor lymphocyte infusion (DLI): 1 achieved CR, 1 PR and 1 had stable disease. Of the 14 patients in group B, 5 received DLI because of relapse/disease progression: 2 obtained PR, and 3 progressed. In conclusion, these findings indicate that graft-versus-myeloma effect appears more effective if HCT is performed earlier after diagnosis in patients with low tumor burden.

Re-Treatment with Rituximab in ITP: Comparison of Standard Dose with 2 Forms of Augmented Rituximab.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1237-1237
Author(s):  
Aisha N. Hasan ◽  
James B. Bussel
Keyword(s):  
Initial Treatment ◽  
Standard Dose ◽  
Similar Response ◽  
Double Dose ◽  
Eligibility Criteria ◽  
Chronic Itp ◽  
Group A ◽  
Group 2 ◽  
Group B

Abstract The purpose of this study was to investigate treatment (tmt) with Rituximab ® in patients (pts) with ITP who had previously received R. Re-treatment (re-tmt) was administered either at standard (std) dose (375 mg/m2 x 4) n=15 or as augmented R, n= 14 (below). Eligibility criteria included primary chronic ITP, platelet count (plt ct)< 30K x 2 within a month, age > 12 years, and prior receipt of std dose R. Augmented R pts were randomised to receive either R-CVP (group A,n=7) or Double Dose R (DDR) (group B,n=7). Group A pts received 1 dose of std dose R 1st and then 3 doses of R-CVP consisting of R, IV doses of Cyclophosphamide 750 mg/m2 & vincristine 1.4 mg/m2 (max 2 mg) and 100 mg prednisone PO daily for 5 days at 3 week intervals. Group B pts were treated with R 750 mg/m2/dose IV weekly for 4 weeks. Pts could receive IVIG during the initial tmt period. Two heavily pre-treated pts did not tolerate R-CVP well and refused the 3rd cycle; 1 std dose pt had an allergic reaction and could not complete her 4th infusion of re-tmt. Otherwise tmt was well tolerated. All pts had decline in circulating CD 19 positive B cells to < 0.03 X 109 and there were no significant decreases in IgG or IgM levels. The table below summarises the response to the various tmts with R. Overview of Response to Initial and Re-treatment with Rituximab Patient 1st Treatment 2nd Treatment DDR/R-CVP ♣ Median Plt. ct Response Median Plt Ct Response Median Plt. Ct Response ♣ 1 270 CR 319 CR 338 CR 2 102 CR 199 CR ♣ 3 157 CR 9 NR 24 NR 4 50 PR 34 PR 52 PR 5 ♣ 50 MR 20 MR ♣ 6 65 PR 25 PR 7 8 NR 25 NR 8 7 NR 15 NR ♣ 9 10 NR 10 NR 10 6 NR 10 NR 11 195 CR 165 CR 12 325 CR 285 CR 267 CR ♣ 13 180 CR 10 NR 14 21 NR 169 CR 15 290 CR 150 CR 16 219 CR 155 CR 17 157 CR 80 PR 18 540 CR 350 CR 19 63 PR 13 NR 20 245 CR 30 NR 21 58 PR 181 CR 22 72 PR 72 PR 23 88 PR 78 PR 24 450 CR 636 CR Among 15 pts on re-tmt with std dose R after ITP relapse, there were 7 complete responses (CR’s) (plt ct > 150,000/ul [150k] for 2 consecutive weeks) and 3 partial responses (PR’s) (plt ct between 50–150k for 2 consecutive weeks). Response to the 1st and 2nd std dose tmt courses was similar (n=15) but 3 pts (#3, 17 & 20 {see table}) with initial CR’s had limited to absent responses to re-tmt. No HAMA or HACA were detected in the 3 pts. With augmented R, there were 3 CR’s among 7 pts randomized to the DDR group (#2, 11, 12). All 3 pts also had CR’s with the 1st tmt. Among 7 pts randomized to the R-CVP group, 1 pt had CR (also had CR with 1st R), 1 had PR (#6) and 4 pts failed to respond altogether; 1 pt just started R-CVP. No pt who did not respond to initial std dose R, responded to either DDR or R-CVP (see figure). 4 pts received re-tmt with std dose R and then augmented R. At this time it does not seem that augmented R has provided additional benefit to these 4 or the other retreated pts. In conclusion, Rituximab re-tmt at std or double dose is well tolerated and generally produces similar response durations to initial R tmt in pts with relapsed chronic ITP. However 3/15 CR pts had no response to re-tmt. Augmented R, either as R-CVP or as DDR, did not provide any clear benefit to pts not responding initially to std R but may be superior to std dose R in some pts. R-CVP was less well tolerated than other regimens. Quality of Response: Comparision of Initial Treatment Vs Re-Treatment with DDR R-CVP Quality of Response: Comparision of Initial Treatment Vs Re-Treatment with DDR R-CVP

Phase 1 study of glutaminase (GLS) inhibitor CB-839 combined with either everolimus (E) or cabozantinib (Cabo) in patients (pts) with clear cell (cc) and papillary (pap) metastatic renal cell cancer (mRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 603-603 ◽  
Author(s):  
Nizar M. Tannir ◽  
Alice C. Fan ◽  
Richard J. Lee ◽  
Bradley Curtis Carthon ◽  
Othon Iliopoulos ◽  
...  
Keyword(s):  
Phase 1 ◽  
Cell Cancer ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Phase 2 ◽  
Eligibility Criteria ◽  
Good Tolerability ◽  
Anti Vegf ◽  
Heavily Pretreated ◽  
Anti Tumor Activity

603 Background: CB-839 is a first-in-class inhibitor of GLS that targets tumor glutamine utilization, a pathway upregulated in kidney cancer. CB-839 combines with E or Cabo in pre-clinical RCC models to inhibit metabolic pathways resulting in enhanced anti-tumor activity. The CX-839-001 study includes cohorts evaluating the safety, efficacy and recommended Phase 2 dose (RP2D) of CB-839 in combination with E (CBE) or Cabo (CB-Cabo) in pts with mRCC. Here we report results from the CBE and CB-Cabo cohorts. Methods: Eligibility criteria included mRCC with cc or pap histology, ECOG 0-1, RECIST measurable disease and, for cc pts, treatment with at least 1 prior anti-VEGF therapy. Pts received escalating doses of CB-839 (PO BID) in a 3+3 design, either 400-800 mg with E (10 mg PO QD) or 600-800 mg with Cabo (60 mg PO QD). Tumor response (RECIST 1.1) was assessed every 8 wks. Results: 27 pts (22 cc, 3 pap, 2 other) were enrolled in CB-E escalation (n = 17) and expansion (n = 10) cohorts (7 at 400 mg, 13 at 600 mg, 7 at 800 mg) and 11 pts (9 cc, 2 pap) in CB-Cabo escalation cohorts (6 at 600 mg, 5 at 800 mg). Median prior lines of therapy was 2 for CBE (including 64% of cc pts with ≥2 prior anti-VEGF therapies) and 3 for CB-Cabo (range 0-6). A maximum tolerated dose was not reached; 800 mg was selected as the RP2D for CB-839. The most common treatment-related Gr≥3 AEs were fatigue (11%), anemia, hyperglycemia, and neutropenia (7% each) for CBE (N = 27) and diarrhea (14%) and platelet count decreased (14% including 1 DLT at 600 mg) for CB-Cabo (N = 7). Of 24 evaluable CBE pts there was 1 PR and 21 SD for a disease control rate (DCR = CR + PR + SD) of 92% with a median PFS of 7.1 mo (95% CI 4 - 11). For 9 evaluable CB-Cabo pts the ORR and DCR were 44% (4 PR) and 100%, respectively. Conclusions: The tumor metabolism inhibitor CB-839 combines with full dose of RCC targeted therapies, E and Cabo, with good tolerability and encouraging clinical activity in heavily-pretreated mRCC pts. CB-Cabo ORR and DCR of 44% and 100% are promising, and CBE DCR of 92% and PFS of 7.1 mo compare favorably to historical E monotherapy. Randomized Phase 2 studies have been initiated (CBE) or are planned (CB-Cabo). Clinical trial information: NCT02071862.

scholarly journals Glioblastoma multiforme in patients over 65 – should we operate?

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv15-iv15
Author(s):  
Igor Maleyko ◽  
Benjamin Hall ◽  
Andrew Brodbelt ◽  
David Lawson ◽  
Michael Jenkinson ◽  
...  
Keyword(s):  
Performance Status ◽  
Age Distribution ◽  
Standard Of Care ◽  
Current Standard ◽  
Eligibility Criteria ◽  
Exact Test ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Radio Chemotherapy

Abstract Aim Current standard of care for glioblastoma is maximum safe resection followed by radio chemotherapy with Temozolomide. Older patients are less likely to receive the full treatment. The aim was to determine treatment and outcomes in glioblastoma patients >65 years. Methods Single centre retrospective study from 2001–2016. Eligible patients had: (i) diagnosis of glioblastoma (ii) undergone biopsy or resection with radiotherapy ± adjuvant chemotherapy. Age at diagnosis, type of surgery, performance status, complications, adjuvant therapy and median survival (MS) were recorded. Patients were assigned to group A (age <65), B (age 65–69 years) or C (age >/= 70 years). Results 637 patients met the eligibility criteria and 403 had complete records for analysis. Age distribution of the cohort was 17.9 – 91.6 years. In the group A (n=259), those who had undergone resection had significantly longer MS compared to biopsy: 17.2 vs 13.2 months (P<0.05 CI: 444.043 – 561.957). 70 patients developed complications. In the group B (n=79), those who had undergone resection had significantly longer MS compared to biopsy: 12.3 vs 5.1 months (P<0.05 CI: 194.354 – 335.646). 17 patients developed complications. In the group C (n=64), analysis did not show statistically significant difference (P=0.066 CI: 220.476 – 321.524). Clinically, patients who had resection had longer MS (10.5 months vs 3.5 months). Furthermore, there was no significant difference in the rate of complications between resection and biopsy (Fisher’s exact test, P=0.755). Conclusion i) Patients >65 should be treated as per the Stupp protocol ii) In patients >70 surgical resection should be considered.:

scholarly journals Phase I Trial of Oral Irinotecan and Temozolomide for Children With Relapsed High-Risk Neuroblastoma: A New Approach to Neuroblastoma Therapy Consortium Study

2009 ◽  
Vol 27 (8) ◽  
pp. 1290-1296 ◽  
Author(s):  
Lars M. Wagner ◽  
Judith G. Villablanca ◽  
Clinton F. Stewart ◽  
Kristine R. Crews ◽  
Susan Groshen ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Phase I Trial ◽  
Single Agent ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Time Curve ◽  
Disease Stabilization ◽  
Heavily Pretreated ◽  
Grade 3

PurposeIrinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma.Patients and MethodsPatients received oral temozolomide on days 1 through 5 combined with oral irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral cefixime was used to reduce irinotecan-associated diarrhea.ResultsFourteen assessable patients received 75 courses. Because neutropenia and thrombocytopenia were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m2/d for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d. First-course grade 3 diarrhea was dose-limiting in one of six patients treated at the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The median SN-38 lactone area under the plasma concentration versus time curve at this dose was 72 ng · hr/mL. One patient with bulky soft tissue disease had a complete response through six courses. Six additional patients received a median of seven courses (range, three to 22 courses) before progression.ConclusionThis all-oral regimen was feasible and well tolerated in heavily pretreated children with resistant neuroblastoma, and seven (50%) of 14 assessable patients had response or disease stabilization for three or more courses in this phase I trial. SN-38 lactone exposures were similar to those reported with protracted intravenous irinotecan. The dosages recommended for further study in this patient population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with cefixime.

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