Phase (Ph) I study of pazopanib (P) in combination with vinorelbine (V) in patients with metastatic non-small cell lung cancer (mNSCLC) and breast cancer (mBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13568-e13568
Author(s):  
Ryan D. Gentzler ◽  
Virginia G. Kaklamani ◽  
Rebekah Worden ◽  
Therese Zumdahl ◽  
Hala D Simm ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Maximum Tolerated Dose ◽  
Vegf Inhibitors ◽  
Free Survival ◽  
Previously Treated ◽  
Dose Levels ◽  
Clinical Trial Information

e13568 Background: V is an established treatment for mNSCLC and mBC, but combination 2nd line chemotherapy has not shown clear benefit for either disease. The anti-VEGF agent bevacizumab improves response rate and progression free survival (PFS) for mNSCLC and mBC. P is a tyrosine kinase inhibitor targeting the VEGF receptors. We hypothesize that because CYP3A4 is inhibited by P and responsible for metabolism of V, there may be synergy between P + V. This is a ph I study testing the combination of P + V in previously treated pts with mNSCLC and mBC. Methods: Pts with Stage IIIB/IV NSCLC or Stage IV mBC with ≤ 2 (lung) or ≤ 3 (breast) prior chemotherapies, no prior VEGF inhibitors, and PS 0-2 were treated with P + V. The objective was to determine the maximum tolerated dose (MTD) of P + V. Dose escalations followed a standard 3+3 design. After 6 pts, the protocol was amended to add an intermittent dosing cohort (2a) to improve tolerability. Response assessment (RA) occurred q 42 days (d) while on study. Pts had weekly toxicity assessments, and PK data was collected on d 1-2 of the first 2 cycles. Results: Eight pts (7 mNSCLC, 1 mBC) were enrolled in 3 of 9 planned cohorts. Pts received a median of 2 cycles. All pts experienced at least 1 grade (gr) 3/4 toxicity. Six dose-limiting toxicities occurred in 4 pts in cohort 2/2a. Five severe adverse events were reported in 4 pts and included thrombocytopenia, neutropenia, abdominal (abd) pain, pneumonia, and hepatotoxicity. Gr 3/4 toxicities were: neutropenia (6), fatigue (2), thrombocytopenia (1), hyperbilirubinemia (1), transaminitis (1), hypertension (1), abd pain (1), and pneumonia (1). 1 pt refused treatment after 1 cycle and had no RA. 5 of 8 pts expired due to progressive disease. No partial responses were noted. Median PFS was 66 d (95% CI 35 to 384 d). Conclusions: Combination of P + V in pre-treated mNSCLC and mBC results in high rates of gr 3/4 toxicities at all dose levels. The trial was suspended due to significant drug-drug interactions before the MTD could be determined. No further study of P in combination with V is warranted in either pt population. Clinical trial information: NCT01060514. [Table: see text]

A phase I study of the combination of sorafenib (Sor) and bortezomib (Bor) in patients (pts) with metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9076-9076 ◽  
Author(s):  
Ryan J. Sullivan ◽  
Nageatte Ibrahim ◽  
Donald P. Lawrence ◽  
Julie Aldridge ◽  
F. Stephen Hodi ◽  
...  
Keyword(s):  
Dose Level ◽  
Tumor Response ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
Expansion Cohort ◽  
Dose Levels ◽  
Clinical Trial Information

9076 Background: Sor is a small molecule tyrosine kinase inhibitor that has many targets and previously was developed for the treatment of MM. Bor is a proteasome inhibitor widely used to treat multiple myeloma and other malignancies. In preclinical studies, the combination of Sor and Bor has been shown to modulate expression of BCL-family members and augment cytotoxicity in MM cell lines. Methods: Pts with MM were enrolled in cohorts of 3 during dose escalation to determine the maximum tolerated dose (MTD) of Sor twice daily (BID) in combination with Bor given days 1, 8, 15 of a 28 day cycle. The MTD was defined as the highest dose level at which less than 33% of pts exhibited a dose limiting toxicity (DLT). Efficacy, as measured by 6-month progression free survival (PFS) and response rate (RR) per RECIST, was documented. Results: Eleven pts were enrolled in 3 dose levels. DLTs (fatigue and rash respectively) were seen in 2 of 3 patients enrolled at the highest dose level (Sor 400 mg and Bor 1.3 mg/m2). The next lowest dose level (Sor 400 BID and Bor 1.0) enrolled 5 pts and none had DLTs. Thus, this dose level was defined as the MTD. Toxicities seen in >20% of pts included hypertension, pruritus, hand-foot syndrome, mucositis, nausea, vomiting, rash, constipation, abdominal pain, anorexia and fatigue. Of 9 response evaluable pts, none had radiographic evidence of tumor response. Two of 11 (18%) pts remained progression free for greater than 6 months. Conclusions: The combination of Sor and Bor is safe, but minimally active in pts with MM. In the absence of tumor response at or above the MTD, the study was closed with only 5 pts treated at the provisional MTD and enrollment to a planned dose expansion cohort will not occur. Clinical trial information: NCT01078961.

TIVO-3: Tivozanib in patients with advanced renal cell carcinoma (aRCC) who have progressed after treatment with axitinib.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 278-278
Author(s):  
Brian I. Rini ◽  
Sumanta K. Pal ◽  
Bernard Escudier ◽  
Michael B. Atkins ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Risk Category ◽  
Vegf Receptor ◽  
Free Survival ◽  
Prior Therapy ◽  
Third Line ◽  
Line Setting ◽  
Clinical Trial Information

278 Background: Tivozanib (T) is a potent and highly selective VEGF receptor (R) tyrosine kinase inhibitor in clinical development for RCC. Axitinib is also a potent and selective VEGF-R inhibitor now commonly part of front-line aRCC treatment. The activity of T after axitinib has not been previously defined. The activity of T after prior therapy types including axitinib is of clinical relevance. Methods: The pivotal TIVO-3 study enrolled subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI, stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized in a 1:1 ratio to T or S. The primary objective of the overall trial was to compare progression free survival (PFS) by blinded independent radiological review. Patients with prior axitinib received as monotherapy in the second or third line setting and other predefined subgroups were reviewed for outcome with T. Results: Patients treated with T after prior axitinib had a PFS of 5.5 months and an ORR of 13% compared to 3.7 months and 8% for patients treated with S. Other subgroups are presented in the table below. Clinical trial information: NCT02627963 . Conclusions: Tivozanib improved PFS vs. sorafenib in patients who have progressed after multiple VEGFR-TKIs, including patients with prior second or third line axitinib treatment. These results suggest differential activity from tivozanib and axitinib despite both being potent and selective VEGF-R inhibitors. [Table: see text]

Decreasing BMI/weight immediately prior to starting anti-PD-1/PDL-1 monoclonal antibodies for treatment for stage IV non-small cell lung cancer is associated with shorter progression-free survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20710-e20710
Author(s):  
Revathi Kollipara ◽  
Ibtihaj Fughhi ◽  
Marta Batus ◽  
Sanjib Basu ◽  
Jeffrey Allen Borgia ◽  
...  
Keyword(s):  
Specific Treatment ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
Negative Change ◽  
Tumor Mutational Burden ◽  
Previously Treated ◽  
Former Smokers ◽  
Nsclc Patients

e20710 Background: Currently, prognostic markers associated with immunotherapy treatment outcomes in patients with metastatic NSCLC include PDL-1 expression, tumor mutational burden (TBM), and neutrophil to lymphocyte ratio (NLR). In this study we examine the influence of pretreatment changes in weight, BMI, and NLR in 237 patients treated with anti-PD-1/PDL-1 therapy (ICI) at our institution. Methods: This was a retrospective analysis of previously-treated stage IV NSCLC patients who received ICI. Pretreatment (≥ 6 weeks before starting therapy) values of weight, BMI, and NLR were compared to baseline values and NLR was analyzed as continuum and according to standard cutoffs of 3.5 and 5. The same variables were correlated with progression-free survival (PFS) and overall survival (OS) using the Log-Rank test. Results: 237 patients were analyzed: 45% were male, 73% were Caucasian, 72% were former smokers, and 25% were age ≥ 75 years. 148 patients had pretreatment NLR values. Of these, 32% had a ratio < 3.5 and 54% had ratio < 5. 34% had increased NLR at baseline, the majority of which (48/77) had a > 5% increase. 187 patients had pretreatment weight and BMI. Of these, 14% had a pretreatment BMI < 20. 71% had a negative change in BMI and 29% had a > 5% decrease in BMI. 65% had a negative change in weight and 26% had a > 5% decrease in weight. BMI decrease greater than 5% (p = 0.0039), negative weight change (p = 0.0371), and pretreatment NLR > 5 (p = 0.0136) were associated with shorter PFS. Change in NLR trended towards decreased PFS but was not statistically significant (p = 0.07) though only 77 of 237 patients had both values available. There was no statistical PFS difference between patients less than or ≥ 75 years old. Conclusions: The results suggest that decrease in pretreatment BMI and weight along with high baseline NLR are associated with significantly shorter PFS in NSCLC treated with anti-PD-1/PDL-1 therapy. If confirmed, these observations raise the possibility that specific treatment which reverses cancer associated weight loss might enhance effectiveness of immunotherapy.

A phase Ib study of abemaciclib in combination with pembrolizumab for patients (pts) with stage IV Kirsten rat sarcoma mutant (KRAS-mut) or squamous non-small cell lung cancer (NSCLC) (NCT02779751): Interim results.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Jean-Louis Pujol ◽  
Johan F. Vansteenkiste ◽  
Luis G. Paz-Ares ◽  
Vanesa Gregorc ◽  
Julien Mazieres ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Open Label ◽  
Free Survival ◽  
Phase 1B ◽  
Clinical Trial Information ◽  
Nonsquamous Nsclc

9562 Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase 4 and 6 inhibitor. In preclinical models, abemaciclib induced intratumor immune inflammation and synergized with PD-1 blockade to enhance antitumor efficacy in anti-PD-L1 refractory disease. Here, we report the safety and antitumor activity of abemaciclib plus the approved NSCLC treatment pembrolizumab in 2 cohorts for pts with nonsquamous and squamous NSCLC. Methods: Eligible pts for this nonrandomized, open-label, multicohort, phase 1b study were either chemotherapy-naive with ≥ 1% tumor cell (TC) PD-L1 staining, KRAS-mut nonsquamous NSCLC (Cohort A) or had a squamous subtype and received ≤ 1 prior platinum-containing chemotherapy regimen (Cohort B) for metastatic NSCLC. Primary endpoint was safety; secondary objectives included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-five pts with NSCLC were enrolled in each cohort. Most pts (68%) in Cohort B had received 1 prior line of chemotherapy. Safety profiles observed in both cohorts were largely consistent with previous reports for abemaciclib and pembrolizumab monotherapy. Grades 3/4 AEs in Cohorts A and B, respectively, included ALT increase (6 pts [24%]/ 0 pts), diarrhea (3 pts [12%]/ 0 pts), neutropenia (3 pts [12%]/ 0 pts), and pneumonitis (3 pts [12%]/ 1 pt [4%]). Six pts in Cohort A (24%) and 2 pts in Cohort B (8%) had a confirmed partial response for a disease control rate (CR+PR+SD) of 52% and 64%, respectively. In Cohort A, the ORR in pts with strong (≥50% TC) PD-L1 staining (n = 13) was 31% vs. 17% in pts with weak (1-49% TC) PD-L1 expression (n = 12). Median PFS and OS were 7.6 months (95% CI: 1.6, NR) and 22.0 months (95% CI: 9.9, NR) in Cohort A and 3.3 months (95% CI: 1.4, 5.2) and 6.0 months (95% CI: 3.7, 13.1) in Cohort B, respectively. Conclusions: Abemaciclib plus pembrolizumab resulted in a numerical higher rate of transaminase elevations and pneumonitis. Antitumor activity was remarkable in the KRAS-mut nonsquamous NSCLC but not noticeably higher as compared to historical data for pembrolizumab monotherapy. Clinical trial information: NCT02779751 .

RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Julie Henriques ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardiere ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

101 Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.

scholarly journals Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial

2016 ◽  
Vol 34 (12) ◽  
pp. 1368-1375 ◽  
Author(s):  
Steven G. DuBois ◽  
Araz Marachelian ◽  
Elizabeth Fox ◽  
Rachel A. Kudgus ◽  
Joel M. Reid ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Phase I Study ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Free Survival

Purpose Alisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population. Patients and Methods Patients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m2 per day on days 1 to 7 along with irinotecan 50 mg/m2 intravenously and temozolomide 100 mg/m2 orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained. Results Twenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m2, with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib. Conclusion Alisertib 60 mg/m2 per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.

Effect of CMP, carfilzomib (CFZ) plus melphalan-prednisone (MP), on response rates in elderly patients (pts) with newly diagnosed multiple myeloma (NDMM): Results of a phase (Ph) I/II trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8513-8513 ◽  
Author(s):  
Cyrille Touzeau ◽  
Brigitte Kolb ◽  
Cyrille Hulin ◽  
Denis Caillot ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Toxicity Profile ◽  
Newly Diagnosed ◽  
Efficacy Data ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Dose Limiting Toxicity ◽  
Clinical Trial Information

8513 Background: MP+thalidomide (MPT) and MP+bortezomib (MPV) have shown significant progression-free survival and overall survival (OS) benefits in NDMM pts > 65 years (y) but are associated with peripheral neuropathy (PN). CFZ, a novel proteasome inhibitor, has shown promising activity and a favorable toxicity profile with low PN rates. Methods: This PhI/II study in NDMM >65y was designed to determine maximum tolerated dose (MTD) of CMP and assess safety and efficacy. In PhI, CFZ was started at 20mg/m2, then escalated to 27, 36, and 45mg/m2, given IV in 42-day (D) cycles (C) on D1/2/8/9/22/23/29/30 for 9C. Melphalan 9mg/m² and prednisone 60mg/m² were given PO D1–4 of every 45-day cycle. MTD was based on dose-limiting toxicity (DLT) in C1 defined as any grade (G) 4 hematologic adverse event (AE), any hematologic AE preventing aministration of ≥ 2 C1 CFZ doses except G4 thrombocytopenia without bleeding or G4 neutropenia ≤7D, ≥G3 febrile neutropenia, or any ≥G3 nonhematologic AE. Results: As of Jan 6, 2013, 24 pts have been enrolled in PhI: 6 for each dose level. There were 2 DLTs at 45mg/m2(fever, hypotension) resulting in a MTD of 36mg/m². In PhII, 45 additional pts received CMP at 36mg/m² CFZ for N=69 total PhI/II pts (median age 74y). ORR was 89% with 51% ≥VGPR. With median follow-up of 12 mo, the projected 2y OS was 89.9%. CMP was well tolerated without PN ≥G2. Conclusions: These results compare favorably to those of MPV, MPT, MP+lenalidomide (R), and R+dex in similar pts (ORR 71% San Miguel NEnglJMed2008, 76% Facon Lancet2007, 80% Palumbo JClinOncol2007 and 85% Rajkumar LancetOncol2010, respectively). CFZ 36mg/m2 +MP is tolerable and effective in elderly NDMM pts. Treatment is ongoing. Final safety and efficacy data will be presented during the meeting. Clinical trial information: NCT01279694.

Phase I study of irinotecan/5-fluorouracil/leucovorin (FOLFIRI) with sunitinib for advanced gastroesophageal cancers (EGC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15569-e15569
Author(s):  
Sarbajit Mukherjee ◽  
Christos Fountzilas ◽  
Patrick McKay Boland ◽  
Kristopher Attwood ◽  
Wei Tan ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Clinical Activity ◽  
Free Survival

e15569 Background: Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor with activity against VEGFR, PDGRF, KIT, FLT-3, and RET. S is synergistic with chemotherapy in preclinical models. We hypothesized that S+FOLFIRI combination will have increased efficacy in advanced EGC. Methods: This was a phase I study for patients with advanced chemo naïve EGC. Dose escalation used a standard 3+3 design. The primary objective was to determine the tolerability and safety of S+FOLFIRI. Secondary objectives were overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Results: Twenty-three patients participated in the study (Male 78%, Female 22%). Median age was 60 (Range: 37-77) years. Median follow up time was 67.5 (95% CI: 58.9, 76) months. The most frequently reported adverse events were neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%) and fatigue (52%; G3/4:17%).Two dose limiting toxicities (DLTs) were noted each at dose level (DL) 1 and 1A, one at DL 1B and 3 at DL 2 (Table 1). Maximum tolerated dose was determined at DL 1B. At the time of data reporting 21 patients had died. Two patients came off the study per investigator request. All patients were evaluated for efficacy. The median OS and PFS were 12.4 (95% CI: 8.9, 16.5) months and 6.2 (95% CI: 3.4, 13.5) months, respectively. Conclusions: S+FOLFIRI was reasonably tolerated, with a manageable safety profile and signs of clinical activity in patients with advanced EGC. This study was supported by a research grant from Pfizer, Inc. Clinical trial information: NCT00524186. [Table: see text]

Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2767-2772 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Free Survival ◽  
Grade 3 ◽  
Dose Levels ◽  
Initial Results

AbstractIn multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.

Clinical Efficacy of Afatinib Treatment for a Patient with Leptomeningeal Carcinomatosis

Chemotherapy ◽  
2016 ◽  
Vol 62 (3) ◽  
pp. 147-150 ◽  
Author(s):  
Yo Kawaguchi ◽  
Jun Hanaoka ◽  
Hideki Hayashi ◽  
Naoki Mizusaki ◽  
Hirotoshi Iihara ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Leptomeningeal Carcinomatosis ◽  
Leptomeningeal Metastases ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Free Survival ◽  
Epidermal Growth ◽  
Egfr Mutated

Leptomeningeal metastases occur in 1% of patients with non-small-cell lung cancer. There have been several reports on the treatment of leptomeningeal metastases with afatinib. Our patient was a 41-year-old woman who had never smoked and was diagnosed with stage IV adenocarcinoma of the lung with an epidermal growth factor receptor (EGFR) mutation. She was treated with afatinib for the recurrence of leptomeningeal metastases. After the treatment with afatinib was initiated, the neurological symptoms dramatically regressed, and she achieved progression-free survival for 7 months. The concentration of afatinib in the cerebrospinal fluid (CSF) ranged from 0.05 to 0.14 ng/mL, and the penetration rate of afatinib from the plasma to the CSF ranged from 0.28 to 0.40%. This concentration might be sufficient to achieve a clinical effect for leptomeningeal carcinomatosis. Therefore, afatinib administered at the usual doses may be an effective treatment for leptomeningeal carcinomatosis of EGFR-mutated or EGFR-tyrosine kinase inhibitor-sensitive lung adenocarcinoma.

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