A targeted supradose cisplatin chemoradiation protocol for advanced head and neck cancer

Robbins, K. Thomas; Vicario, Daniel; Seagren, Stephen L.; Weisman, Robert A.; Pellitteri, Phillip K.; Kerber, Charles W.; Orloff, Lisa A.; Los, Gerritt; Howell, Stephen B.

doi:10.1016/s0002-9610(05)80089-3

Cited by 171 publications

(84 citation statements)

References 19 publications

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“…dose on day 1 only. Figure 4 shows the effect of these doses on the growth of the 2008 human ovarian carcinoma xenograft when treatment was delivered at the point that the median tumor volume was f75 mm 3 . In this model, oxaliplatin had no discernable activity whereas even a single dose of AP5346 produced long-lasting inhibition of tumor growth.…”

Section: Resultsmentioning

confidence: 99%

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Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

Rice¹,

Gerberich²,

Nowotnik³

et al. 2006

Clinical Cancer Research

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103

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Purpose: AP5346 is designed to target a diaminocyclohexane platinum (Pt) moiety to tumors through pH-sensitive linkage to a 25 kDa hydroxypropylmethacrylamide polymer. The goal of these studies was to determine the rate of release of Pt as a function of pH, the antitumor activity, and plasma and tumor pharmacokinetics of AP5346 in preclinical models. Experimental Design: Antitumor activity was assessed in mice bearing B16F10 melanoma and M5076 and 2008 ovarian carcinomas. Pt levels in plasma, tumors, and tumor DNA were measured by atomic absorption and inductively coupled plasma mass spectrometry. Results: AP5346 did not release Pt when suspended in 5% dextrose and released only 3.5% of its Pt in 24 hours in buffer at pH 7.4; the rate of release was 7-fold higher at pH 5.4. When given at their respective maximum tolerated doses, the antitumor activity of AP5346 was superior to that of oxaliplatin against both the B16 melanoma and 2008 human ovarian carcinoma. It was more effective than cisplatin in both cisplatin-sensitive and cisplatin-resistant variants of the M5076 tumor. When given at equitoxic doses, the peak plasma concentration was 25-fold higher, and AUC (0-1) was 93 times higher, for AP5346 than for oxaliplatin. AP5346 delivered 16.3-fold more Pt to the tumor and 14.2-fold more Pt to tumor DNA than oxaliplatin based on AUC . Conclusions: AP5346 has a substantially better therapeutic index than oxaliplatin. AP5346 produced a marked increase in the delivery of diaminocyclohexane Pt to the tumor and tumor DNA over and above that attainable with oxaliplatin.

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Section: Resultsmentioning

confidence: 99%

“…Similarly, modest 2-to 3-fold increases in Pt delivery to squamous cell carcinomas of the head and neck can be achieved by giving very large doses of cisplatin intraarterially in combination with i.v. sodium thiosulfate to protect the systemic circulation (2), and this approach has been shown to increase response rates (3).…”

mentioning

confidence: 99%

Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

Rice¹,

Gerberich²,

Nowotnik³

et al. 2006

Clinical Cancer Research

Self Cite

103

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“…Following on from their initial work, Robbins et al [38] evaluated the response to treatment in 29 patients with previously untreated stage IV disease and observed complete pathologic responses in 23/24 evaluated patients (96%). Grade III or IV chemotoxicities occurred after only 14 of the 110 infusions carried out during the study (12.7%).…”

Section: Study Outcomesmentioning

confidence: 99%

RADPLAT: An Alternative to Surgery?

2006

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Head and neck cancer frequently presents at a late stage, leading to a poor prognosis despite optimal treatment with surgery and/or radiotherapy. Chemotherapy for advanced disease has shown little benefit as a single-modality treatment, and the use of concurrent chemoradiation is limited by problems with severe toxicity at higher doses. RADPLAT is the acronym used to describe a new technique, combining intra-arterial delivery of cisplatin with systemic neutralization by i.v. sodium thiosulphate, and concurrent radiotherapy. This allows very high cisplatin dose intensities to be used while potentially minimizing adverse systemic effects. Initial results suggest that excellent locoregional control rates are achievable in patients with unresectable disease, with a favorable side-effect profile when compared with conventional chemoradiation protocols. In addition, RADPLAT may potentially be of benefit in selected patients with resectable disease, allowing for preservation of organ function and quality of life without compromising locoregional control or survival. While current phase II data are encouraging, phase III randomized controlled trials are required in order to directly compare RADPLAT with i.v. chemoradiation therapy, the current standard of care. This article reviews the evolution of the RADPLAT concept, from initial clinical trials to its current application in the treatment of patients with advanced head and neck cancer.

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“…The systemic toxicity of RADPLAT is less severe than that of standard systemic chemotherapy protocols [5,6]. Previously, we reported the efficacy of our modified protocol of RADPLAT, termed the Kanazawa regimen (cisplatin 150 or 100 mg/body intra-arterially (IA) and STS 14 g/m 2 intravenously (IV), two to three courses, radiotherapy 2 Gy/fraction, 66 Gy).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer

Ishikawa

Sugimoto

Hatano

et al. 2015

Acta Oto-Laryngologica

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Conclusions: Intra-arterial high-dose cisplatin chemoradiation (CRT-IA) with sodium thiosulfate (STS) causes relatively less severe cisplatin ototoxicity than intravenous cisplatin chemoradiation without STS (CRT-IV). The results of this study also suggest that early detection of ototoxicity is possible by testing the hearing loss at ultra-high frequencies. Objectives: To investigate protective effects of STS against cisplatin ototoxicity. Methods: Between 2011 and 2013, 18 patients with head and neck carcinomas were treated with intra-arterial infusions of high-dose cisplatin (range 100-180 mg/body, mean 111 mg/body; range 2-5 courses, mean 3.6 courses) and systemic administration of cisplatin (range 66-185 mg/body, mean 130 mg/body; range 1-3 courses, mean 2.6 courses) and concurrent radiation therapy (range 60-70 Gy, mean 69 Gy). Cisplatin was neutralized by STS in CRT-IA but not in CRT-IV. Results: Intra-arterial infusion in the high-dose cisplatin group caused significant hearing loss at ultra-high frequencies of 10 and 12 kHz (p = 0.028, 0.039, respectively), whereas the group receiving systemic administration of cisplatin had significant hearing loss at high frequencies of 8 and 10 kHz (p = 0.016, 0.027, respectively).

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A targeted supradose cisplatin chemoradiation protocol for advanced head and neck cancer

Cited by 171 publications

References 19 publications

Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor-Targeting Drug Delivery System

RADPLAT: An Alternative to Surgery?

Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer

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