Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors.
Clin Cancer Res
; 24(1): 43-51, 2018 01 01.
Article
en En
| MEDLINE
| ID: mdl-29030354
ABSTRACT
Purpose:
NC-6004, a novel cisplatin nanoparticle developed using micellar technology exhibits sustained release of cisplatin and selective distribution to tumors. Preclinical data demonstrated a favorable tolerability profile and preserved or improved antitumor activity compared with cisplatin across animal models. We evaluated the safety and tolerability of NC-6004 and gemcitabine using a Bayesian continual reassessment model (N-CRM) to determine the optimal dose.ExperimentalDesign:
Patients with advanced solid tumors received NC-6004 at 60 to 180 mg/m2 on day 1 and gemcitabine at 1,250 mg/m2 on days 1 and 8 every 3 weeks. Dose escalation of NC-6004 began with a single patient run-in until a dose-limiting toxicity occurred at 180 mg/m2 Cohorts of four patients were enrolled at doses predicted by the N-CRM. The maximum tolerated dose (MTD) was defined as having the greatest probability of target toxicity <25%. Quality of life was assessed using EORTC-QLQ-C30.Results:
Among 22 patients, the most common grade III/IV hematologic adverse events were leukopenia (68%) and thrombocytopenia (59%). Of 20 pretreated patients evaluable for response, half were previously exposed to a platinum agent. The MTD was 135 mg/m2 Nine patients were treated at the MTD with median treatment duration of 15 weeks (range, 3-50). Tumor shrinkage occurred in 11 (55%), partial responses in 3 (15%), and stable disease in 14 (70%). Most patients reported stable or improved EORTC QLQ-C30 scores.Conclusions:
Greater cisplatin equivalent doses were achieved with no clinically significant neuro-, oto-, or nephrotoxicity. These data demonstrate tolerability and promising activity of NC-6004 in combination with gemcitabine. Clin Cancer Res; 24(1); 43-51. ©2017 AACR.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Aspecto:
Patient_preference
Límite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article