Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jul 2010
Case ReportsCisplatin administration following carboplatin desensitization failure in primary peritoneal cancer: a brief report.
Platinum-based therapy is the cornerstone of ovarian cancer treatment. Development of platinum hypersensitivity can limit therapeutic options. In this brief report, we present case of successful cisplatin administration following two unsuccessful carboplatin desensitization attempts, and without the need for pre-treatment steroids. ⋯ Platinum-based therapies are vital to the treatment of primary peritoneal and ovarian carcinoma. Protocols that successfully incorporate platinum agents, despite a platinum hypersensitivity, are clinically relevant.
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Cancer Chemother. Pharmacol. · Jul 2010
Phase I dose-escalation study of brostallicin, a minor groove binder, in combination with cisplatin in patients with advanced solid tumors.
Brostallicin is a DNA minor groove binder which shows enhanced antitumor activity in cells which are resistant to several anticancer agents due to their high glutathione S-transferase (GST)/glutathione content. Phase I and II clinical trials of single-agent brostallicin have shown that myelotoxicity is the dose-limiting toxicity (DLT), while hints of antitumor activity were mainly observed in soft tissue sarcoma. Preclinical studies showing a more than additive antitumor effect of the cisplatin-brostallicin combination paved the way to clinical combination studies. In particular, we set up the first clinical combination study of brostallicin and cisplatin in patients with advanced solid tumors. This study was to be followed by a phase II study in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). ⋯ Further studies of the combination of brostallicin and cisplatin are warranted.
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Cancer Chemother. Pharmacol. · May 2010
Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor-expressing tumor models.
The folate receptor (FR) is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery of anti-cancer agents to FR-expressing tumors. Targeting liposomes to the FR has been proposed as a way to enhance the effects of liposome-based chemotherapy. ⋯ Folate-targeting confers a significant albeit modest therapeutic improvement to PLD in FR-expressing tumor models, which appears particularly valuable in intracavitary therapy. The potential clinical added value of this approach has yet to be determined.
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Cancer Chemother. Pharmacol. · Apr 2010
Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates.
Cisplatin, carboplatin, and oxaliplatin are chemically reactive anticancer drugs with modest activity in brain tumors. Previously, we have demonstrated that drug exposure in cerebrospinal fluid (CSF) for these platinum analogs is <5% of the plasma ultrafiltrate (UF) drug exposure in nonhuman primates. Microdialysis is a minimally invasive in vivo method for sampling small molecules in the blood and tissue extracellular fluid (ECF). The purpose of this study was to estimate the penetration of platinum analogs into the brain ECF. ⋯ The penetration of platinum analogs into CSF and brain is limited. The differences in the CNS penetrations among the three platinum analogs are not clinically significant. For cisplatin and carboplatin, CSF penetration appears to be a surrogate for brain extracellular free drug exposure.
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Cancer Chemother. Pharmacol. · Mar 2010
Safety, tolerability, and pharmacokinetics of the anti-IGF-1R monoclonal antibody figitumumab in patients with refractory adrenocortical carcinoma.
Insulin-like growth factor 1 receptor signaling through upregulation of the stimulatory ligand IGF-II has been implicated in the pathogenesis of adrenocortical carcinoma. As there is a paucity of effective therapies, this dose expansion cohort of a phase 1 study was undertaken to determine the safety, tolerability, pharmacokinetics, and effects on endocrine markers of figitumumab in patients with adrenocortical carcinoma. ⋯ The side effect profile and pharmacokinetics of figitumumab were similar in patients with adrenocortical carcinoma in comparison to patients with other solid tumors. While hyperglycemia was the most common adverse event, no clear patterns predicting severity were observed. The majority of patients receiving protocol therapy with single agent figitumumab experienced stability of disease, warranting further evaluation.