Phase Ib/II study of INNO-206 (EMCH-doxorubicin) in patients with soft tissue sarcoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10036-10036 ◽  
Author(s):  
Sant P. Chawla ◽  
Victoria S Chua ◽  
Andrew Hendifar ◽  
Doris Quon ◽  
Sandeep Nagre ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Tumor Response ◽  
Acid Reflux ◽  
Hematological Toxicity ◽  
Cardiac Ultrasound ◽  
Standard Doxorubicin ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity ◽  
Unacceptable Toxicity

10036 Background: The safety and preliminary tumor response of a doxorubicin conjugate, INNO-206, was evaluated primarily in patients with metastatic STS who progressed on prior chemotherpy. INNO-206 consists of doxorubicin attached to an acid-sensitive linker that binds covalently to cysteine-34 in circulating albumin. Methods: INNO-206 was administered IV at doses of either 230, 350 and 450 mg/m2 (165, 260 and 325 mg/m2 dox. eq.) every 21 days for up to 8 consecutive cycles. Subsequent dose levels were administered if < 2/5 or 4/8 patients experienced a non-hematological dose-limiting toxicity during Cycle 1. Tumor response was monitored every other month and treatment continued until tumor progression or unacceptable toxicity. Standard safety monitoring was performed and cardiac function was followed periodically using MUGA or cardiac ultrasound. Results: As of January 11, 2012, 25 patients were entered in the study. 21/25 patients had STS of various types. Of the 5 patients treated at 230 mg/m2 INNO-206, 1 subject had grade 3 fatigue and acid reflux. Of the initial 5 patients entered at the 350 mg/m2 dose, no individuals experienced a grade 3 or 4 non-hematological toxicity during cycle 1. 2 patients treated at the 450 mg/m2 dose developed grade 3 oral mucositis during cycle 1. No patient exhibited cardiotoxicity as determined by MUGA or cardiac ultrasound. The MTD was determined to be 350 mg/m2 INNO-206 (260 mg/m2 dox.eq.). 15 more patients were entered at this dose (total of 20 patients). Of the 16 patients with STS, 3 objective partial responses (one of whom received prior doxorubicin) are ongoing as well as 10 patients with stable disease (range 2-7 months). 1 patient had progressive disease at the first evaluation. 2 patients died within the first cycle, one due to progressive disease and the other due to sepsis. Conclusions: INNO-206 is an active drug for the treatment of patients with advanced STS who have failed prior chemotherapy. Cumulative doses of 2000 mg/m2 of doxorubicin equivalents have been achieved, which is over 3 1/2 x the peak cumulative dose of standard doxorubicin. Adverse events are primarily hematological and no cardiotoxicity has been observed.

A phase I study of TPI287: A third generation taxane administered weekly in patients with advanced cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2575-2575
Author(s):  
J. J. Hwang ◽  
J. L. Marshall ◽  
T. Ahmed ◽  
H. Chun ◽  
M. Basche ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Progressive Disease ◽  
Phase 1 ◽  
Human Tumor ◽  
Dose Escalation Study ◽  
The Face ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity ◽  
Mdr 1

2575 Background: TPI 287 is an investigational taxane designed to not be a substrate for mdr-1 and to bind to mutant tubulin. In preclinical studies, TPI 287 demonstrated activity against multiple human tumor xenografts in nude mice, including xenografts that expressed mdr-1 and that were resistant to other taxanes. The safety and tolerability of TPI 287 when administered weekly for 3 weeks followed by a 1 week rest (4 week cycle) was examined in this Phase 1 dose escalation study in patients (pts) with advanced neoplasms. Materials and Methods: TPI 287 was administered over 1 hour weekly for 3 weeks followed by 1 week of no treatment. Treatment cohorts consisted of 3 pts and were expanded to 6 pts in the face of dose-limiting toxicity (DLT); pts could remain on study until the development of progressive disease or an intolerable adverse event. DLT was defined as Gr 4 heme toxicity lasting 7 days; febrile neutropenia, Gr 3 thrombocytopenia with bleeding, Gr 3 elevation of transaminases lasting 7 days or any other Gr 3/4 toxicity other than nausea or vomiting. Results: 25 pts (M:F 16:9, median age 60, range 24 - 86) were enrolled in 7 dose levels ranging from 7–185 mg/m2. Pts’ cancers included colorectal (6 pts); NSCLC (2); prostate (2); squamous cell carcinoma (2) and 1 pt each with cervical, breast, ovarian, gastric, pancreatic, bladder endometrial, NSCLC, SCLC, glioblastoma, melanoma, renal cell and hepatocellular carcinoma. All pts but 1 had received prior chemotherapy (median no. prior treatments: 3 (range, 1–7). Drug related adverse events included nausea, vomiting, diarrhea, fatigue, anorexia, rash, anemia and peripheral neuropathy. 1 pt., who was inadvertently treated with inadequate marrow reserve, experienced Gr 4 neutropenia and died of sepsis. DLT of Grade 3 peripheral neuropathy has been observed. PK data to date reveal that AUC is generally dose linear. At a dose of 127.5 mg/m2, clearance was 30.2 + 11.9 L/hr/m2 and t1/2 8.6 + 1.3 hrs. Results are similar with non-compartmental methods and 2-compartment modeling. Conclusions: TPI 287 can be safely administered in doses of up to 127.5 mg/m2 weekly x 3. No significant financial relationships to disclose.

Feasibility of an adapted schedule of carboplatin plus paclitaxel in elderly women with advanced ovarian cancer: A retrospective cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5546-5546
Author(s):  
Benjamin Nicaise ◽  
Soraya Mebarki ◽  
Mathilde Gisselbrecht ◽  
Elisabeth Ashton ◽  
Henri Azais ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Progressive Disease ◽  
Elderly Women ◽  
Advanced Ovarian Cancer ◽  
Early Discontinuation ◽  
Grade 3 ◽  
Vulnerable Elderly ◽  
Dose Delay ◽  
Dose Reductions ◽  
Unacceptable Toxicity

5546 Background: The EWOC-1 trial compared Carboplatin monotherapy (C mono) to two different Carboplatin + Paclitaxel (CP) regimens (weekly or 3-weekly) in vulnerable elderly patients treated for advanced ovarian cancers (OC). This study was closed prematurely because of a worse outcome in the C mono group. Both CP regimens were equivalent in terms of feasibility and efficacy with different toxicity profiles. Optimal CP regimen in elderly patient is still unknown. Here we propose a study of another adapted regimen of CP (aCP) performed in elderly patients in our institution. Methods: We retrospectively analyzed OC patients ≥ 70 years who received a Carboplatin AUC 4-5 d1q3week + Paclitaxel 80 mg/m² d1-d8 q3week regimen between 2015 and 2019. Primary endpoint was treatment feasibility according to the EWOC-1 standard: completion of 6 courses of chemotherapy without early stopping for disease progression, death or unacceptable toxicity (adverse event (AE) related to chemotherapy or treatment procedure leading either to early treatment stopping, to an unplanned hospital admission or to death or to a dose delay lasting more than 14 days or more than 2 dose reductions). Results: We identified 36 pts with a median age of 79 years (table). All patient but one had an ONCODAGE-G8 score ≤ 14, 30.6% of patients had a comorbidity Charlson’s index > 4 and 52.5% had an albumin rate < 35 g/L. The feasibility endpoint was met in 58.3% of patients (IC95% = [25.6; 57.8]). Main causes of treatment failure (TF) were early discontinuation because of toxicity in 6 patients (16.7%) and progressive disease in 3 patients (8.33%). Median PFS was 35.3 months (IC95% = [22.7; NR]) and median OS was 62.1 months (IC95% = [31.4.0; NR]). The most frequent AE were asthenia (all grades = 94.4%, grade 3-4 = 13.9%), anemia (all grades = 94.4%, grade 3-4 = 27.8%), neutropenia (all grades = 66.7%, grade 3-4 = 38.9%) and neuropathy sensory (all grades = 61.1%, no grade 3-4). Non high-grade-serous histological type and a poor Charlson’s score were associated with a higher rate of TF (100% and 63.6%, respectively). Conclusions: These results are consistent with the findings of the EWOC-1 trial in both CP regimens and suggest that aCP could be non-inferior with an acceptable toxicity profile. Further prospective and comparative studies are mandatory to confirm this trend and to better identify predictive factors of TF in OC elderly patients.[Table: see text]

scholarly journals Efficacy of combination-chemotherapy with pirarubicin, ifosfamide, and etoposide for soft tissue sarcoma: a single-institution retrospective analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shiro Saito ◽  
Hisaki Aiba ◽  
Satoshi Yamada ◽  
Hideki Okamoto ◽  
Katsuhiro Hayashi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Events ◽  
Combination Chemotherapy ◽  
Progressive Disease ◽  
Treatment Phase ◽  
Hematological Toxicity ◽  
Single Institution ◽  
Grade 3

Abstract Background The standard chemotherapy regimens for soft tissue sarcoma are doxorubicin-based. This retrospective study aimed to assess the efficacy and safety of pirarubicin, ifosfamide, and etoposide combination therapy for patients with this disease. Methods Between 2008 and 2017, 25 patients with soft tissue sarcoma were treated with pirarubicin (30 mg/m2, 2 days), ifosfamide (2 g/m2, 5 days), and etoposide (100 mg/m2, 3 days) every 3 weeks. The primary endpoint was overall response, and the secondary endpoint was adverse events of this regimen. Results Responses to this regimen according to RECIST criteria were partial response (n = 9, 36%), stable disease (n = 9, 36%) and progressive disease (n = 7, 28%). During the treatment phase, frequent grade 3 or worse adverse events were hematological toxicities including white blood cell decreases (96%), febrile neutropenia (68%), anemia (68%), and platelet count decreases (48%). No long-term adverse events were reported during the study period. Conclusion This regimen was comparable to previously published doxorubicin-based combination chemotherapy in terms of response rate. Although there were no long-lasting adverse events, based on our results, severe hematological toxicity should be considered.

Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.

1998 ◽  
Vol 16 (9) ◽  
pp. 3037-3043 ◽  
Author(s):  
H S Nicholson ◽  
M Krailo ◽  
M M Ames ◽  
N L Seibel ◽  
J M Reid ◽  
...  
Keyword(s):  
Phase I ◽  
Children And Adolescents ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Cancer Group ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity

PURPOSE The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI). PATIENTS AND METHODS Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily. RESULTS Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up. CONCLUSION The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.

A Phase 1 Study of Concomitant High Dose Lenalidomide and 5-Azacytidine Induction in the Treatment of Acute Myeloid Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3616-3616
Author(s):  
Giridharan Ramsingh ◽  
Peter Westervelt ◽  
Amanda Cashen ◽  
Geoffrey L. Uy ◽  
Keith Stockerl-Goldstein ◽  
...  
Keyword(s):  
Complete Remission ◽  
Progressive Disease ◽  
Phase 1 ◽  
Hematological Toxicity ◽  
High Dose ◽  
Phase 2 ◽  
Elderly Aml ◽  
Grade 3 ◽  
Induction Cycle ◽  
Refractory Aml

Abstract Abstract 3616 Novel therapies for elderly and relapsed AML are needed. We recently published an institutional phase 2 trial using high dose (50mg/day × 28 days) single agent lenalidomide (HDL) followed by maintenance of 10 mg daily for 12 months in responders in elderly untreated AML patients (≥ 60 years) showing a complete remission (CR)/complete remission with incomplete blood count recovery (CRi) of 30% (Fehniger et al, Blood, 2011). Azacitidine (AZA) given IV or SC has also shown significant response in patients with MDS and AML. Recently Pollyea et al (JCO 29: 2011 (suppl; abstr #6505) reported on a phase 1 trial combining AZA and escalating doses of lenalidomide repeated sequentially in 6 week cycles in patients with untreated AML. Here, we report on a phase 1 single institutional study to evaluate the toxicities and feasibility of combining HDL and AZA concurrently as induction followed by a less intensive lenalidomide and AZA maintenance schedule in untreated elderly AML (≥60 years) or relapsed/refractory AML ≥18 years. Treatment schedule: 2 cycles of induction (each 28 days) of lenalidomide 50 mg PO days 1–28 and AZA at 3 dose cohorts 25 mg/m2 (cohort 1), 50 mg/m2 (cohort 2) and 75 mg/m2 (cohort 3) given IV days 1–5. Thereafter patients were given maintenance cycles (every 28 days) with lenalidomide 10 mg PO days 1–28 and AZA 75 mg/m2 days 1–5 for a total of 12 cycles. The median age was 74 (range 63–81); 7 males, 8 females; 6 with newly diagnosed elderly AML and 9 with relapsed or refractory AML. The median WBC count was 2600 (range 300–13100). The median bone marrow blast percentage was 22% (range 2–90%),with normal cytogenetics in 7 (63.6%), monosomy 7 in 3 (20%), trisomy 8 in 1 (6.7%), and other in 4 (26.6%). 8 patients were enrolled in cohort 1, 4 patients in cohort 2 and 3 patients in cohort 3. 2 patients in cohort 1 and 1 patient in cohort 2 who received less than 1 induction cycle (2 withdrew consent and 1 had progressive disease) were replaced. 11 (73.3%) of patients completed 1 induction cycle and 7 (46.7%) of patients completed 2 induction cycles and 5 (30%) patients went on to maintenance therapy. Patients remained on therapy for a median of 2 months (range 0.5–13 months). Dose limiting toxicities (DLT) observed included grade 3 rash in cohort 1 leading to expansion of the cohort to include 3 additional patients. To date grade 3/4 non-DLT hematological toxicity was seen in 6/11 (54.1%) patients. The most common 3/4 non-DLT non-hematological toxicity was neutropenic fever seen in 5/11 (45.4%). The most common grade 1/2 toxicity was fatigue in 7/11 (63.6%). 40% (6/15) of patients died, all due to progressive disease. Of the 11 evaluable patients 7 (63.6%) responded to treatment with CR/CRi in 3 (27.3%) and partial remission (PR) in 4 (36.4%) with the median duration of response of 3 months (range 0.5–11 months). In summary combination of lenalidomide with AZA appears to be a feasible regimen with acceptable toxicities. A phase 2 multicenter extension of this study with untreated elderly AML at the maximum tolerated dose of AZA and HDL will be initiated soon. Disclosures: Off Label Use: Here we discuss the use of lenalidomide and azacytidine in relapsed refractory or elderly AML. Stockerl-Goldstein:Celgene: Speakers Bureau. Vij:Celgene: Consultancy, Research Funding, Speakers Bureau.

A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12024-12024
Author(s):  
P. Kumar ◽  
M. Keshtgarpour ◽  
H. Kumar ◽  
A. Dudek
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Tumor Types ◽  
Dose Levels

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]

Phase I study of erlotinib (E) for solid tumors in patients with hepatic or renal dysfunction (HD or RD): CALGB 60101

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3026-3026
Author(s):  
A. A. Miller ◽  
D. J. Murry ◽  
D. R. Hollis ◽  
K. Owzar ◽  
L. D. Lewis ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Progressive Disease ◽  
Performance Status ◽  
Direct Bilirubin ◽  
Hematologic Toxicity ◽  
Renal Obstruction ◽  
Reduced Dose ◽  
Grade 3 ◽  
Tolerable Dose ◽  
Dose Limiting Toxicity

3026 Background: We sought to determine a tolerable dose and characterize the pharmacokinetics (PK) of E in patients with HD or RD. Methods: Patients with biopsy-proven solid tumors that commonly express EGFR, refractory to or without available standard therapy, performance status 0–2, and without biliary or renal obstruction were assigned to one of 3 cohorts (C): C1, AST ≥ 3 × ULN but no RD; C2, direct bilirubin 1–7 mg/dl but no RD; C3, creatinine 1.6–5.0 mg/dl but no HD. After slow accrual of 3 patients, an amended C1 for albumin < 2.5 g/dl accrued 3 additional patients. E was administered po daily in groups of at least 3 evaluable patients in escalating doses of 50, 75, 100, 150 mg starting with 50 mg in HD and 75 mg in RD. Patients had to take E for at least 4 weeks to be considered evaluable for toxicity unless dose-limiting toxicity (DLT) occurred sooner. DLT was defined as: grade 4 neutrophils or platelets; bilirubin ≥ 1.5 × baseline in C1/2 and ≥ 2.5 × ULN in C3; creatinine ≥ 2 × ULN in C1/2 and ≥ 2.5 × baseline in C3; grade ≥ 3 nausea,vomiting,diarrhea despite optimal supportive care; or any other grade ≥ 3 non-hematologic toxicity. Blood samples were obtained before and 1, 2, 3, 4, 6, 24 hrs after the first dose. Plasma E concentrations were measured by HPLC. A 2-compartment PK model was used to estimate total clearance of E. Results: Between 12/01 and 5/05, 55 patients were accrued but 1 never started therapy: male/female, 34/20; white/black, 46/8; median age 56 (range, 39–78); PS 0/1/2, 12/25/17. The distribution of treated/evaluable patients was: 6/5 in C1, 30/16 (attrition due to progressive disease) in C2, and 18/18 in C3. DLT consisted of both total and direct bilirubin ≥ 1.5 × baseline in 3 patients: C1, 1 of 5 at 50 mg; C2, 2 of 6 at 100 mg. In C2, 1 of 7 patients had grade 4 diarrhea/dehydration and grade 3 hypotension at 75 mg. No DLT was encountered in C3 with 12 patients at 150 mg. Clearance (mean ± SD) was cohort-dependent: 1.51 ± 0.64 (C1), 2.36 ± 1.17 (C2), 4.34 ± 2.53 (C3) l/hr; 2-sided exact Kruskal-Wallis p < 0.0006. Conclusions: Patients with RD tolerate 150 mg and appear to have normal clearance of E. Patients with HD should be treated at a reduced dose (i.e. 75 mg) consistent with their reduced clearance. [Table: see text]

Pemetrexed and carboplatin in the treatment of malignant pleural mesothelioma (MPM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18114-18114
Author(s):  
M. Papi ◽  
G. Genestreti ◽  
D. Tassinari ◽  
E. Tamburini ◽  
S. Nicoletti ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Locally Advanced ◽  
Median Number ◽  
Hematological Toxicity ◽  
Complete Regression ◽  
Progression Of Disease ◽  
Localized Disease ◽  
Grade 3 ◽  
Vitamin B12 Supplementation ◽  
Unacceptable Toxicity

18114 Background. MPM is a poor prognosis disease, whose clinical negative outcome is due both to it’s aggressiveness and to the lack of active drugs for clinical practice. To assess activity and safety of pemetrexed-carboplatin combination in the treatment of MPM, an open trial has been recently concluded in our departments. Methods. All the consecutive patients with proven diagnosis of MPM admitted to our departments between 2003 and 2005 were considered eligible and enrolled into the trial. All the patients were treated with pemetrexed 500mg/m2 and carboplatin AUC 5mg/ml/minute every 21 days until progression of disease or unacceptable toxicity. All the patients were treated with steroid prophylaxis, folinic acid and vitamin B12 supplementation. Results. 26 patients (18 chemotherapy-naive) were considered eligible and enrolled into the trial. 21 patients were male and 5 female; median age of the patients was 67 years (range 49–77). 22 patients were affected by locally advanced or extensive disease and the other 4 ones by localized disease. All the patients were valuable for response, toxicity and survival. Overall response rate was 19,3%, with 5 partial responses and no complete regression of the disease. A stable disease was observed in 7 patients (26.9%), with an overall disease control rate of 46.2%. 201 complete courses of chemotherapy was performed with a median number of 6 courses/patients. Toxicity was mild with grade 3/4 WHO neutropenia in 4 patients (15.3%), grade 3 anemia and thrombocytopenia in 2 patients (7.6%). No grade 3/4 non-hematological toxicity was observed along all the conduction of the trial. Median survival was 9,3 months, assessed with the Kaplan Meyer non-parametric test. Conclusions. Pemetrexed and carboplatin seem to represent an active and well tolerated schedule against MPM, confirming their priority role in the treatment of the disease; nevertheless, further trials are probably needed to improve the outcome of chemotherapy in this rare poor-prognosis disease. Supported by IOR No significant financial relationships to disclose.

Phase I trial of zalutumumab and irinotecan in metastatic colorectal cancer patients who have failed irinotecan- and cetuximab-based therapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15028-e15028
Author(s):  
M. Mano ◽  
A. Hendlisz ◽  
J. Machiels ◽  
E. Ehrnrooth ◽  
H. Aladdin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pulmonary Embolism ◽  
Phase I Trial ◽  
Maximum Tolerated Dose ◽  
Heavily Pretreated ◽  
Human Igg1 ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Dose Limiting Toxicity ◽  
Unacceptable Toxicity

e15028 Background: Zalutumumab is a novel human IgG1 anti-EGFR mAb. We investigated the safety of zalutumumab and irinotecan in heavily pretreated mCRC patients. Methods: Metastatic CRC patients with documented progression (PD) during or within 6 months of stopping cetuximab and irinotecan based therapy were eligible. No prior treatment with anti-EGFR antibodies other than cetuximab was allowed. Patients received weekly doses of zalutumumab 8mg/kg and 16 mg/kg respectively in combination with irinotecan (180 mg/m2) every second week until PD or unacceptable toxicity. Results: The maximum tolerated dose was not reached and no patients experienced any dose limiting toxicity. At data cut-off (18-Dec-08) 4 patients had died (no cases of death were considered related to zalutumumab), 4 were off study due to PD and 1 was still ongoing ( Table 1 ). In total, 6 patients experienced one or more grade 3/4 toxicities (diarrhea 2; neutropenia 2; leucopenia 1; abdominal pain 1; pulmonary embolism 1; alopecia 1). Conclusions: Zalutumumab can be safely administrated in doses up to 16mg/kg in combination with irinotecan in mCRC patients failing cetuximab and irinotecan based therapy. Zalutumumab and irinotecan resulted in durable stable disease warranting further investigation of this regimen. [Table: see text] [Table: see text]

Phase I trial of docetaxel (D), cisplatinum (C), and continuous capecitabine (CAP) (TCX) in advanced esophagogastric cancer (AEC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14587-e14587
Author(s):  
Simon Gollins ◽  
Arwel Lloyd ◽  
Jackie Morris ◽  
Nick Smith ◽  
Brian Haylock ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Free Survival ◽  
Best Response ◽  
Esophagogastric Cancer ◽  
Grade 3 ◽  
Dose Levels ◽  
Dose Limiting Toxicity

e14587 Background: This phase I study assessed the combination of D, C, and continuous CAP in AEC to develop a regimen of acceptable toxicity to take forward to phase II study. Methods: Patients with AEC were treated in cohorts of 3, at one of 3 dose levels (DL). DL0: D at 60 mg/m2 IV on day 1, C at 60 mg/m2 IV on day 1, CAP at 1,000 mg/m2 per day in two divided doses days 1-21, every 3 weeks. DL1: CAP increased to 1,250 mg/m2 per day. DL2: D increased to 75 mg/m2 IV day 1 and CAP to 1,250 mg/m2 per day. Prophylactic colony stimulating factors were not used. Patients received a maximum of 6 cycles. Blood counts and biochemistry were assessed twice weekly and daily for grade 3/4 abnormality. Results: Between 1.11.07 and 24.6.09 15 patients were enrolled: male/female:14/1, WHO PS:0/1:10/5, median age 63 yr (range 46-69), primary site oesophagus/GOJ/stomach:7/3/5, adeno/squamous:14/1, T2/3/4:2/9/4, N0/1/2:1/13/1, M0/1:1/14. 6 patients were treated at DL0, 6 at DL1 and 3 at DL2. All patients received 6 cycles apart from 2 at DL 1 who received 3 because of disease progression. Dose intensity: DL0: D 95%, C 100%, CAP 85%; DL1: D 91%, C 98.2%, CAP 79%; DL2: D 86%, C 100%, CAP 79%. There were no deaths on chemotherapy or within 30d of the last dose. The main dose limiting toxicity was febrile or infective neutropenia developing in 1/6 DL0, 2/6 DL1 and 3/3 DL2 (see table of most common treatment-related adverse events below: serious toxicity is gr 3 unless specified gr 4). The maximum length of gr 4 neutropenia was 5d. Best response (RECIST): 1 CR, 11PR, 2 SD and 1PD. 11 patients received second-line chemotherapy. Median and 1 yr overall survival: 17.5m and 60%. Median and 1 yr progression-free survival: 7m and 27%. Conclusions: TCX DLO is recommended for further study in a phase II trial. Encouraging response and survival were seen. [Table: see text]

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