Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung

Bart P H Wittgen, Peter W A Kunst, Kasper Van Der Born, Atie W. Van Wijk, Walter Perkins, Frank G. Pilkiewicz, Roman Perez-Soler, Susan Nicholson, Godefridus J. Peters, Pieter E. Postmus

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Abstract

Purpose: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma. Experimental Design: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course. Results: Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%), dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle). Conclusions: Aerosolized liposomal cisplatin was found to be feasible and safe.

Original languageEnglish (US)
Pages (from-to)2414-2421
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number8
DOIs
StatePublished - Apr 15 2007

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Inhalation
Cisplatin
Carcinoma
Lipids
Lung
Lung Volume Measurements
Therapeutics
Pharmacokinetics
Tracheostomy
Forced Expiratory Volume
Carbon Monoxide
Safety
Compassionate Use Trials
Hoarseness
Bronchitis
Respiratory Function Tests
Platinum
Dyspnea
Nausea
Vomiting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wittgen, B. P. H., Kunst, P. W. A., Van Der Born, K., Van Wijk, A. W., Perkins, W., Pilkiewicz, F. G., ... Postmus, P. E. (2007). Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clinical Cancer Research, 13(8), 2414-2421. https://doi.org/10.1158/1078-0432.CCR-06-1480

Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. / Wittgen, Bart P H; Kunst, Peter W A; Van Der Born, Kasper; Van Wijk, Atie W.; Perkins, Walter; Pilkiewicz, Frank G.; Perez-Soler, Roman; Nicholson, Susan; Peters, Godefridus J.; Postmus, Pieter E.

In: Clinical Cancer Research, Vol. 13, No. 8, 15.04.2007, p. 2414-2421.

Research output: Contribution to journalArticle

Wittgen, BPH, Kunst, PWA, Van Der Born, K, Van Wijk, AW, Perkins, W, Pilkiewicz, FG, Perez-Soler, R, Nicholson, S, Peters, GJ & Postmus, PE 2007, 'Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung', Clinical Cancer Research, vol. 13, no. 8, pp. 2414-2421. https://doi.org/10.1158/1078-0432.CCR-06-1480
Wittgen BPH, Kunst PWA, Van Der Born K, Van Wijk AW, Perkins W, Pilkiewicz FG et al. Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. Clinical Cancer Research. 2007 Apr 15;13(8):2414-2421. https://doi.org/10.1158/1078-0432.CCR-06-1480
Wittgen, Bart P H ; Kunst, Peter W A ; Van Der Born, Kasper ; Van Wijk, Atie W. ; Perkins, Walter ; Pilkiewicz, Frank G. ; Perez-Soler, Roman ; Nicholson, Susan ; Peters, Godefridus J. ; Postmus, Pieter E. / Phase I study of aerosolized SLIT cisplatin in the treatment of patients with carcinoma of the lung. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 8. pp. 2414-2421.
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abstract = "Purpose: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma. Experimental Design: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course. Results: Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7{\%}), vomiting (47.1{\%}), dyspnea (64.7{\%}), fatigue (64.7{\%}), and hoarseness (47.1{\%}). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle). Conclusions: Aerosolized liposomal cisplatin was found to be feasible and safe.",
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AU - Perkins, Walter

AU - Pilkiewicz, Frank G.

AU - Perez-Soler, Roman

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AU - Peters, Godefridus J.

AU - Postmus, Pieter E.

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