Phase I study of bortezomib with weekly paclitaxel in patients with advanced solid tumours

• Published in: European journal of cancer (1990) Vol. 44; no. 13; pp. 1829 - 1834
• Main Authors: Cresta, S, Sessa, C, Catapano, C.V, Gallerani, E, Passalacqua, D, Rinaldi, A, Bertoni, F, Viganò, L, Maur, M, Capri, G, Maccioni, E, Tosi, D, Gianni, L
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-2008; Elsevier
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Boronic Acids - administration & dosage; Boronic Acids - adverse effects; Bortezomib; Breast Neoplasms - drug therapy; Clinical study; Combination; Female; Hematology, Oncology and Palliative Medicine; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Ovarian Neoplasms - drug therapy; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Pharmacology. Drug treatments; Phase I; Prostatic Neoplasms - drug therapy; Proteasome inhibitor; Pyrazines - administration & dosage; Pyrazines - adverse effects; Solid tumours; Taxane; Treatment Outcome; Tumors; Weekly paclitaxel; Phase I; Weekly paclitaxel; Bortezomib; Solid tumours; Proteasome inhibitor; Combination; Taxane; Clinical study; Antineoplastic agent; Human; Solid tumor; Malignant tumor; Cancerology; Treatment; Analog; Taxane derivatives; Paclitaxel; Dipeptides; Phase I trial; Advanced stage; Antimitotic; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2008.05.022

Abstract Background The combination of a proteasome inhibitor with a taxane has potential clinical synergism that prompted a clinical test. Patients and methods The maximum tolerated dose (MTD) and recommended dose (RD) of intravenous (i.v.) Bortezomib (B) (days 1, 4, 8, 11) and i.v. Paclitaxel (PTX) (days 1, 8) every 3 weeks was evaluated in patients with advanced solid tumours. The RD was tested in patients with breast, ovarian and prostate cancer. At the RD, microarray analysis of transcriptional profiles was carried out before and after the first dosing in peripheral blood mononuclear cells (PBMC). Results Thirty-one patients were enrolled and 22 were treated at the RD that corresponded to B 1.3 mg/m2 and PTX 100 mg/m2 . The main toxicity was cumulative peripheral neuropathy (76% of patients; grade 3–4 in 9%) that required treatment discontinuation in six patients, followed by diarrhoea (55%) and fatigue (41%). Nine partial responses (30%) were observed (three breast cancer, four ovary, two prostate patients). Significant ( p < 0.05) and consistent changes (>70% of patients) in transcriptome were observed. Conclusions The incidence of peripheral neuropathy and the anti-tumour activity comparable to that of single-agent PTX do not support further development of this regimen.