Phase I trial of extrapleural pneumonectomy [EPP], and intracavitary intraoperative hyperthermic [IOHC] cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. [MPM]

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18059-18059
Author(s):  
L. Zellos ◽  
W. G. Richards ◽  
L. Capalbo ◽  
M. Jaklitsch ◽  
R. Bueno ◽  
...  
Keyword(s):  
Chest Wall ◽  
Median Survival ◽  
Renal Toxicity ◽  
Multimodality Treatment ◽  
Maximum Tolerated Dose ◽  
Extrapleural Pneumonectomy ◽  
Innovative Strategies ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Stage 1

18059 Background: Despite aggressive multimodality treatment, MPM remains a disease with poor survival. Innovative strategies that improve cytoreduction are needed. We sought to determine the maximum tolerated dose (MTD) and quantify the toxicity of cisplatin IOHC with amifostine cytoprotection in the setting of EPP for MPM. Methods: 42 MPM patients (pts) were enrolled in an IRB approved protocol. Those who underwent EPP with cytoreduction to < 1 cm3 received 910 mg/m2 of amifostine followed by 1-hour perfusion of the chest and abdomen with cisplatin dose escalation (75–200 mg/m2). Pts were monitored prospectively. Results: 13 pts were unresectable (9 with chest wall invasion, 3 with chest wall and mediastinal invasion and 1 with cardiac invasion). The 29 resected pts had median age 57 years; median stay 15 days, and mortality rate 6.8% (2/29 pts.). Complications were: atrial fibrillation 65.5% (19 pts.), deep vein thrombosis 31% (9 pts.), and grade 3 renal toxicity 31% (9 pts.). Renal toxicity was unrelated to cisplatin dose and no MTD was determined. Median follow-up was 17 months. Median survival (MS) for 42 enrolled pts was 17 months. The 13 unresected pts experienced a 10-month MS. The 29 resected pts had a 20-month MS while 24 epithelial pts experienced a 29-month MS and 5 non-epithelial pts 13 month MS (p=0.006). The 15 pts receiving higher cisplatin doses (175–200 mg/m2) had a 26-month MS while the 14 pts receiving lower doses (75–150 mg/m2) had 16-month median survival. (p=NS) The 10 pts with negative margins has a MS of 25.8 months while 19 pts with positive margins had a 13.4 month MS (p=NS). MS for 20 pts with N2 (-) nodes was 30 months and for 9 pts with N2 (+) 13 months (p= 0.0115). MS for 18 pts with BWH/DFCI stage 1–2 was 32 months and for the 11 stage 3 pts 14 months (p=0.0022). Conclusions: 1) IOHC was technically feasible with acceptable morbidity and mortality 2) Single dose amifostine was inadequate against cisplatin renal toxicity and MTD was not determined. 3) Stage 1–2, epithelial type or N2 (-) pts demonstrated survival greater that expected historic controls. No significant financial relationships to disclose.

Safety and pharmacokinetics (PK) of AMG 706 in combination with gemcitabine for the treatment of patients (pts) with solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14005-14005 ◽  
Author(s):  
T. J. Price ◽  
L. Lipton ◽  
J. Williams ◽  
J. McGreivy ◽  
S. McCoy ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Vein Thrombosis ◽  
Finding Study ◽  
Label Dose ◽  
Grade 3 ◽  
Deep Vein

14005 Background: AMG 706 is an oral, investigational multikinase inhibitor (MKI) with antiangiogenic and direct antitumor activity achieved by selectively targeting VEGF, PDGF and Kit receptors. Methods: This is a fully enrolled, phase 1b, open-label, dose- finding study. The objectives are to determine the maximum tolerated dose and to assess safety and PK of AMG 706 in pts with solid tumors receiving AMG 706 plus gemcitabine. Pts =18 years with ECOG 0–2 and no prior treatment with bevacizumab or VEGFr MKIs were assigned to cohorts receiving escalating doses of AMG 706 (50mg QD, 125mg QD or 75mg BID continuously from day 2 of cycle 1) plus gemcitabine (1000mg/m2 weekly for 7/8 wks, then 3/4 wks per cycle) for up to 11 cycles. Assessments include dose-limiting toxicities (DLT) (weeks 1–4) and tumor response (every 3 months). Results: 26 pts were enrolled and received at least 1 dose of AMG 706 (50mg QD n=11; 125mg QD n=6; 75mg BID n=9). All but 2 pts have completed the study. Median (range) age was 57 (25–77) yrs. 65% of pts received prior chemotherapy; 4 pts received prior gemcitabine (50mg QD n=2; 125mg QD n=1; 75mg BID n=1). There were 2 DLTs: grade 4 neutropenia (125mg QD), grade 3 deep vein thrombosis (75mg BID). Treatment-related adverse events (AE) occurring in = 10% of pts are shown in the table . The mean AMG 706 PK profiles were not markedly different when AMG 706 was dosed on the same day or 24 hours after gemcitabine administration. Objective tumor responses per RECIST for 26 evaluable pts were: 2 unconfirmed PR (50mg QD n=1; 125mg QD n=1), 7 SD (50mg QD n=3; 125mg QD n=1; 75mg BID n=3), 11 PD (50mg QD n=7; 125mg QD n=3; 75mg BID n=1), and 6 not available (125mg QD n=1; 75mg BID n=5). Conclusions: These preliminary data suggest that, in pts with solid tumors, AMG 706 combined with gemcitabine had an expected AE profile at the target once-daily dose of 125mg QD, with little effect on AMG 706 PK. The data provide a foundation for conducting further trials, potentially including biliary tumors. Final data will be presented. [Table: see text] No significant financial relationships to disclose.

Safety and early efficacy results from a phase I study of volociximab (V) in combination with carboplatin (C) and paclitaxel (P) in patients (pts) with advanced non small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13513-e13513
Author(s):  
B. Besse ◽  
S. Almokadem ◽  
D. Planchard ◽  
I. Chico ◽  
C. L. Tsao ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Arterial Occlusion ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Open Label ◽  
Dose Escalation Study ◽  
Vein Thrombosis ◽  
Label Dose ◽  
Grade 3 ◽  
Peripheral Arterial

e13513 Background: Volociximab is a chimeric monoclonal antibody that blocks fibronectin binding to α5β1 and induces apoptosis in proliferating endothelial cells. Its anti-angiogenic actions are independent of the VEGF pathway. This is the first clinical study of voloxicimab in patients with advanced NSCLC. Methods: This phase 1b multi-center open-label, dose-escalation study was designed to determine the maximum tolerated dose of V in combination with full doses of C (AUC=6mg/ml.min) P (200mg/m2) with cycles repeated every 3 wks for a maximum of 6 cycles followed by a maintenance treatment with V alone. Eligible pts had histologically confirmed untreated stage IIIb or IV NSCLC. In cohorts 1 and 2, pts received V at 10 mg/kg and 20mg/kg IV, respectively, on days 1 and 8, of the first 21 day cycle then every 21 days. In cohort 3, pts received V 30 mg/kg IV every 21 days from day 1. We present here the interim safety analysis and RECIST response data of the combination therapy. Results: A total of 22 patients (9, 6 and 7 in cohorts 1, 2 and 3 respectively) who received at least one dose of treatment constitute the safety population. Reported salient adverse events (any grade) were constipation (68%), asthenia (64%), nausea (59%), arthralgia (55%) and paresthesia (46%). Grade 3 bowel obstruction in one patient was considered a DLT in cohort 2. No DLT's were observed in cohort 3. Seven pts reported at least one serious adverse event (all Grade 3) including deep vein thrombosis (1), peripheral arterial occlusion (1), proteinuria (1), pneumonitis (1), small intestinal obstruction (1), pleural effusion (1), hypoxia (1), dehydration (1) and orthostatic hypotension (1). Partial response was seen in 6 pts and stable disease in 12 out of 18 pts who were evaluable for response by RECIST. Conclusions: The highest dose of V tested (30 mg/kg q3w) in combination with CP appears well tolerated and the regimen has promising clinical activity in advanced NSCLC. [Table: see text]

Phase Ib/IIa study of GC1118 in combination with irinotecan or FOLFIRI in patients with metastatic solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3592-3592
Author(s):  
Keun Wook Lee ◽  
Sae-Won Han ◽  
Ji-Won Kim ◽  
Dae-Won Lee ◽  
Yong Sang Hong ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Skin Rash ◽  
Single Agent ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Stage Design ◽  
Phase 1B ◽  
Grade 3 ◽  
Stage 1

3592 Background: GC1118 is a novel anti-EGFR monoclonal antibody which has a unique binding epitope and superior ligand inhibition potential. It showed promising antitumor activity as a single agent in the phase I study. This study aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of GC1118 in combination with irinotecan or FOLFIRI in metastatic solid tumors and evaluate the efficacy of GC1118 plus FOLFIRI as a second line therapy for RAS and BRAF wild-type metastatic colorectal cancer. Methods: Phase 1b part was designed to evaluate weekly GC1118 (starting from 3 mg/kg) in combination with biweekly irinotecan (180mg/m2) or FOLFIRI (irinotecan 180mg/m2, leucovorin 400mg/m2, 5-FU 400 mg/m2 bolus, and 5-FU 2400mg/m2 over 46hrs) in a 3+3 design. In the phase 2a part, the RP2D of GC1118 is administered in combination with FOLFIRI in a Simon’s two stage design with objective response rate (ORR) as the primary endpoint. Results: 13 pts were enrolled in phase 1b and received 3mg/kg of GC1118 with irinotecan (N = 6) or FOLFIRI (N = 7). DLT occurred in 2 pts (G4 neutropenia, G2 rash) in irinotecan arm and 1pt (G3 neutropenia) in FOLFIRI arm with 3mg/kg of GC1118 and it was determined as MTD and RP2D. Adverse events (AE) of grade ≥ 3 included neutropenia (61.5 %), skin rash (15.4 %) and diarrhea (15.4%). Dose reductions due to GC1118-related AE were required in 6 (46.2%) patients. Among 10 response-evaluable pts in phase 1b, best overall response was PR in 3 and SD in 6, and median PFS was 12 months. In stage 1 of phase 2a (N = 9), 4 PR and 5 SD were observed (ORR 44.4%, 95% CI 13.7 – 78.8). We moved to stage 2, and are currently enrolling additional 20 pts. AE of grade ≥ 3 included neutropenia (66.7%), skin rash (22.2%) and diarrhea (11.1%). Updated data of the phase 2a part will be presented at the meeting. Conclusions: The MTD and RP2D of weekly GC1118 in combination with irinotecan or FOLFIRI was 3mg/kg. Preliminary results of GC1118 and FOLFIRI as a 2nd line treatment in mCRC suggests promising antitumor activity and acceptable safety profile. Clinical trial information: NCT03454620 .

Evaluation of patupilone as monotherapy in patients with advanced hepatocellular carcinoma (HCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15055-15055 ◽  
Author(s):  
A. P. Venook ◽  
R. Poon ◽  
Y. K. Kang ◽  
T. S. Mok ◽  
Y. Chao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Stage 1

15055 Background: Currently, there is no strong evidence that systemic therapies provide a survival benefit for patients (pts) with hCC. However, preclinical data have shown that the novel epothilone patupilone has potent anti-proliferative activity against 8 HCC cell lines with intrinsic multidrug resistance. This exploratory study tested whether patupilone monotherapy has antitumor activity in HCC patients with intact liver function. Methods: This open-label, single-arm, multicenter, 2-stage phase II study was to enroll 24 pts in the first stage and 41 pts in the second stage, if = 3 complete or partial responses were observed in the first stage. Patients with unresectable and/or metastatic HCC (histologically confirmed) with = 1 measurable lesion were eligible if they had well-preserved hepatic function (Child-Pugh Class A) and life expectancy = 3 months. Patupilone was administered as a single IV infusion at 10 mg/m2 over 20 minutes every 3 weeks. Primary endpoint was objective response. Results: Twenty-five patients were enrolled, 24 were evaluable, and 1 violated protocol. The most common adverse events (AEs) suspected to be study-drug related were NCI CTC grade 1/2 diarrhea, fatigue, and vomiting. Grade 4 serious AEs included hyponatremia (2 pts [8%]), cardiac arrest (1 pt [4%]), diarrhea (1 pt [4%]), and gastrointestinal hemorrhage (1 pt [4%]). Grade 3 serious AEs included diarrhea (3 pts [12%]), hyponatremia (2 pts [8%]), deep vein thrombosis (1 pt [4%]), abdominal pain (1 pt [4%]), and hyperkalemia (1 pt [4%]). Most pts had dose adjustments or delays; 3 discontinued treatment. During the first stage, 1 pt had a confirmed partial response through 4 cycles, and 11 pts (44%) had stable disease for = 2 cycles with a median of 4 cycles (range, 2 to 8 cycles). Median progression-free survival was 3 months (range, 1 to 6 months), and 10 pts (40%) progressed within the first 2 cycles. The study did not progress to stage 2. Conclusions: Patupilone demonstrated an acceptable safety profile. Serious AEs were observed in a minority of patients, and most did not require treatment discontinuation. Patupilone demonstrated only modest antitumor activity in pts with HCC in this study. No significant financial relationships to disclose.

The role of extrapleural pneumonectomy in the management of pleural cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7577-7577
Author(s):  
D. J. Sugarbaker ◽  
T. R. Tilleman ◽  
S. J. Swanson ◽  
M. T. Jaklitsch ◽  
S. J. Mentzer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Survival ◽  
Sarcomatoid Carcinoma ◽  
Retrospective Chart Review ◽  
Multimodality Treatment ◽  
Stage Iiib ◽  
Extrapleural Pneumonectomy ◽  
Final Pathology ◽  
Pleural Metastases

7577 Background: We report our experience with EPP for non-mesothelial malignancies. Methods: A retrospective chart review, from June 1994 to October 2007. For all cases, the site of disease involved a single pleura. Results: Sixty-five patients underwent EPP for cancers other than mesothelioma over a 13-year period at our institution. Of these, 32 patients had mediastinoscopy negative T4 lung cancer, 11 had metastases to only one pleura from extrathoracic sites, 10 had unilateral lung sarcomas involving the pleural envelope, 8 had thymomas metastatic to a pleural space, 2 were preoperatively diagnosed as mesotheliomas but at final pathology were determined to be small cell lung cancer and sarcomatoid carcinoma, and 2 represented primary mucoepidermoid and neuroectodermal malignancies. Twenty-eight patients had stage IIIB (T4-N0–1) lung adenocarcinoma representing the largest homogeneous group of patients by cell type and stage. Overall perioperative mortality was 4.6% (3/65). Postoperative morbidity was 44.6% (29/65) with the most common being arrhythmia (n=15), vocal cord paralysis (n=7), and respiratory failure (n=5). Overall survival after surgery was 15.7 months for all the patients. Survival was significantly higher for NSCLC patients with N0 (n=9) on final pathology versus any other nodal status (N1/N2), 52.1 months versus 14.1 months (p=0.0003). Median survival for stage IIIB NSCLC was 16.7 months. Seven of the 8 thymoma patients were alive at last follow-up (median follow-up 22.8 months). Median survival for patients with sarcoma (n=10) or pleural metastases from extrathoracic sites (n=11) was 3.7 and 4.2 months, respectively. Recurrence at follow-up was documented in 21 patients with only 2 (9.5%) occurring in the ipsilateral hemithorax. Conclusions: EPP can be a safe treatment option for some cancers that involve a unilateral pleura. Patients with stage IIIB (T4, N0–1) NSCLC confined to a single pleural cavity or patients with thymoma involving one pleura may benefit from multimodality treatment including EPP. Absence of residual nodal disease at resection is positively correlated with survival in the stage IIIB NSCLC group. Patients undergoing surgical resection for pleural metastases of primary sarcomas or extrathoracic metastasis, however, do not appear to benefit from EPP. No significant financial relationships to disclose.

Phase I trial of radiotherapy with concurrent bevacizumab, erlotinib, and capecitabine for locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 254-254
Author(s):  
Heath Devin Skinner ◽  
Milind M. Javle ◽  
Robert A. Wolff ◽  
Marilyn V. Clemons ◽  
Mark F. Munsell ◽  
...  
Keyword(s):  
Median Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
High Rate ◽  
Viable Tumor ◽  
Grade 3 ◽  
Dose Levels

254 Background: The addition of bevacizumab to capecitabine-based chemoradiotherapy (CRT) for LAPC has been shown to be safe. The aim of this study was to determine the safety, tolerability and maximum tolerated dose (MTD) of the addition of erlotinib to this treatment regimen. Methods: Seventeen patients with CT-staged biopsy-proven non-metastatic unresectable LAPC were enrolled between March 2008 and October 2010. Prior chemotherapy was permitted. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose was escalated using a continual reassessment method. Two patients each were enrolled at dose levels (DLs) 1-4 and 9 patients at DL 5. Bevacizumab was escalated from 5mg/Kg every two weeks (DLs 1-4) to 10mg/Kg (DL 5); erlotinib from 100 mg/day (DLs 1-2) to 150 mg/day (DLs 3-5); and capecitabine from 400mg/m2 twice daily on days of radiation (DL 1) to 600mg/m2 (DLs 2-3) to 825 mg/m2 (DLs 4-5). Reassessment for potential resection was performed 6-8 weeks later. Results: With a median follow-up of 10 months (range 3-23), no grade 3 toxicities were observed in DLs 1-4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrheas and 1 rash). No grade 4 or 5 toxicities were seen. DL 4, with a posterior probability of 0.122 of dose limiting toxicity, was selected as the MTD. Median survival was 19.4 months and time to distant progression was 9.8 months. Patients treated at DLs 4 and 5 had a median survival of 24 months. Of 5 patients who underwent margin-negative resections, 4 were originally deemed unresectable and 1 was borderline; 4 were treated at DLs 4 or 5 (36% of patients treated at these DLs); 3 patients had excellent pathological responses (complete response, 5% viable tumor, and 20% viable tumor) at pancreatectomy and are alive at 13, 21 and 22 months respectively with no local or distant failures. Conclusions: The combination of erlotinib, bevacizumab and capecitabine with radiotherapy for LAPC is safe and tolerable. Both the promising survival and the high rate of resectability at the higher dose levels suggest that this strategy of dual inhibition of growth factor receptor pathways during CRT warrants continued evaluation.

MM-005: A phase I trial of pomalidomide, bortezomib, and low-dose dexamethasone (PVD) in relapsed and/or refractory multiple myeloma (RRMM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8584-8584
Author(s):  
Paul Gerard Guy Richardson ◽  
Craig C. Hofmeister ◽  
David Samuel DiCapua Siegel ◽  
Sagar Lonial ◽  
Jacob Laubach ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Response Duration ◽  
Maximum Tolerated Dose ◽  
Phase Iii ◽  
Clinical Activity ◽  
Vein Thrombosis ◽  
Duration Of Response ◽  
Grade 3 ◽  
Expansion Cohort

8584 Background: Combinations of lenalidomide (LEN), bortezomib (BORT), and dexamethasone (DEX) have demonstrated preclinical and clinical activity in patients (pts) with multiple myeloma. Pomalidomide with low-dose DEX (LoDEX) has demonstrated efficacy in RRMM pts treated with prior LEN and BORT. MM-005 was designed to identify the optimal PVD dose for a phase 3 trial comparing PVD vs BORT + LoDEX (VD) in RRMM (MM-007). Methods: Eligible pts had RRMM with 1-4 prior therapies including ≥ 2 consecutive cycles of LEN and a proteasome inhibitor. Pts must have been refractory to LEN (progressive disease [PD] during or within 60 days of LEN treatment), but not refractory to BORT (at 1.3 mg/m2 twice-weekly). The maximum tolerated dose (MTD) was determined using a 3 + 3 design in 5 cohorts. Each cohort received 21-day cycles of POM 1-4mg/day on D1-14; BORT 1-1.3mg/m2on D1, 4, 8, 11; and LoDEX 20mg/day on D1-2, 4-5, 8-9, 11-12. An expansion cohort was enrolled at the MTD. Treatment was continued until PD or unacceptable toxicity. Dose-limiting toxicities (DLTs) were assessed during cycle 1. The primary endpoint was MTD; secondary endpoints were safety, overall response rate (ORR; ≥ partial response), duration of response, and time to response (TTR). Results: As of Dec 31, 2012, 21 pts were enrolled (3 pts per escalating dose cohort; 6 in the expansion cohort). Median age was 57 years (36-75). All were LEN-refractory and had prior BORT. No DLTs were observed at any dose level. The most common grade 3/4 adverse events (AEs) were neutropenia (32%) and thrombocytopenia (21%). With thromboprophylaxis, no deep vein thrombosis was observed. 17 pts remain on study and no pts have discontinued treatment due to AE. Thus far, the ORR was 72% (n = 18 evaluable) and responses were rapid (median TTR, 2 cycles). Conclusions: PVD was well-tolerated in RRMM with no DLTs and no discontinuations due to AE to date. PVD has promising activity with a current ORR of 72%. The maximum planned dose of POM 4mg/day on D1-14; BORT 1.3mg/m2 on D1, 4, 8, and 11; and DEX 20mg on D1-2, 4-5, 8-9, 11-12 of a 21-day cycle has now been incorporated into the MM-007 phase III trial comparing PVD with VD in RRMM pts (N = 782 planned). Clinical trial information: NCT01497093.

Safety and pharmacokinetics (PK) of AMG 706 with panitumumab plus FOLFIRI or FOLFOX for the treatment of patients (pts) with metastatic colorectal cancer (mCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4081-4081 ◽  
Author(s):  
L. S. Schwartzberg ◽  
H. Hurwitz ◽  
J. Stephenson ◽  
D. Kotasek ◽  
D. Goldstein ◽  
...  
Keyword(s):  
Tumor Response ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Open Label ◽  
Prior Chemotherapy ◽  
Prior Therapy ◽  
Vein Thrombosis ◽  
Finding Study ◽  
Label Dose ◽  
Grade 3

4081 Background: AMG 706 is an oral, investigational multikinase (MKI) inhibitor with antiangiogenic and direct antitumor activity, selectively targeting VEGF, PDGF and Kit receptors. Methods: This is an ongoing phase 1b, open-label, dose-finding study of AMG 706 with panitumumab plus FOLFIRI or FOLFOX in pts with mCRC. Objectives are to establish safety, PK, and the maximum tolerated dose of AMG 706 with this regimen. Pts =18 yrs with mCRC, ECOG 0–1, =1 prior chemotherapy for advanced disease and no prior oral VEGFr MKIs or anti-EGFR therapy, received either FOLFIRI or FOLFOX (based on prior therapy) plus panitumumab (6mg/kg IV day 1 of each 2-wk cycle), and escalating doses of AMG 706 (50, 75, 125mg QD; 75mg BID) given continuously from day 3 of cycle 1. Assessments included dose-limiting toxicities (DLT) during the first 2 cycles and tumor response (every 6–8 wks from wk 6). Results: As of Nov 2006, 45 pts were enrolled and received at least 1 dose of AMG 706 (FOLFIRI/FOLFOX n=33/12); 64% had prior chemotherapy. There were 6 DLTs: FOLFIRI n=4, all grade 3 (diarrhea n=2: 50mg QD, 75mg BID; deep vein thrombosis n=1: 75mg QD; high GI output n=1: 75mg BID); FOLFOX n=2 (all fatigue, grade 3: 50mg QD). Treatment-related adverse events (AE) occurring in =10% of pts included: any AE, FOLFIRI/FOLFOX 88/92% of pts (grade 3, 21/58%); fatigue 55/58% (12/33%), anorexia 24/50% (0/0%), diarrhea 24/33% (0/8%), epistaxis 27/0% (0/0%) and hypertension 15/8% (0/0%). There were no grade 4/5 AEs. 2 cases of cholecystitis (grade 3, n=1) occurred. Preliminary data showed that AMG 706 PK at 50mg QD (FOLFOX) and 50–125mg QD (FOLFIRI) was comparable to data from monotherapy studies at the same dose levels. AMG 706 did not markedly alter the PK profiles of irinotecan or its metabolites. Objective tumor response per RECIST is shown in the table . Conclusions: In this study of pts with mCRC, AMG 706 was tolerable when combined with panitumumab and FOLFIRI or FOLFOX, with little effect on AMG 706 PK. [Table: see text] No significant financial relationships to disclose.

scholarly journals Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma

Leukemia ◽  
2017 ◽  
Vol 31 (12) ◽  
pp. 2695-2701 ◽  
Author(s):  
P G Richardson ◽  
C C Hofmeister ◽  
N S Raje ◽  
D S Siegel ◽  
S Lonial ◽  
...  
Keyword(s):  
Proteasome Inhibitor ◽  
Low Dose ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Dose Escalation Study ◽  
Vein Thrombosis ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3 ◽  
Deep Vein

Abstract This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1–4 mg days 1–14), bortezomib (1–1.3 mg/m2 days 1, 4, 8 and 11 for cycles 1–8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2 and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.

scholarly journals Surgical Management and Reconstruction of Diaphragm, Pericardium and Chest Wall in Mesothelioma Surgery: A Review

2021 ◽  
Vol 10 (11) ◽  
pp. 2330
Author(s):  
Pietro Bertoglio ◽  
Elena Garelli ◽  
Jury Brandolini ◽  
Kenji Kawamukai ◽  
Filippo Antonacci ◽  
...  
Keyword(s):  
Chest Wall ◽  
Multimodality Treatment ◽  
Surgical Approaches ◽  
Extrapleural Pneumonectomy ◽  
Parietal Pleura ◽  
Reconstruction Technique ◽  
Cardiac Herniation ◽  
Respiratory Impairment ◽  
Chest Wall Recurrence ◽  
Invasive Techniques

Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.

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