Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies

Shimada, Muneaki; Fujiwara, Hiroyuki; Sato, Shinya; Oishi, Tsutomu; Itamochi, Hiroaki; Machida, Shuichi; Takei, Yuji; Harada, Tasuku; Suzuki, Mitsuaki; Kigawa, Junzo

doi:10.1007/s00280-012-1885-z

Cited by 5 publications

(1 citation statement)

References 16 publications

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“…There was also a relationship between the observed AUC and the relative reduction ratio of platelets, although the dose of nedaplatin based on body surface area did not relate to the relative reduction ratio of platelets (Figure 6). We also confirmed that the observed AUC corresponded to the target AUC by dosing based on renal function, although there was no relationship between the observed AUC and Dose NDP (mg/m 2 ) based on body surface area 16. Consequently, our two previous clinical evaluations suggested that Ishibashi’s formula would be predictable and useful for estimating the individual dose of nedaplatin.…”

Section: Optimal Dosage Based On Renal Functionsupporting

confidence: 73%

Nedaplatin: a cisplatin derivative in cancer chemotherapy

Shimada¹,

Itamochi²,

Kigawa³

2013

CMAR

Self Cite

104

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Nedaplatin, a cisplatin analog, has been developed to decrease the toxicities induced by cisplatin, such as nephrotoxicity and gastrointestinal toxicity. The dose of nedaplatin is determined by body surface area, not by the area under the curve (AUC). The recommended therapeutic dose is 80–100 mg/m2, although the pharmacokinetic profile of nedaplatin is similar to that of carboplatin. In our preliminary study, there was a favorable correlation between AUC and creatinine clearance (CL), suggesting that renal function should be considered when nedaplatin is administered. Ishibashi’s formula, ie, DoseNDP = AUC × CLNDP, where CLNDP = 0.0738 × creatinine clearance + 4.47, would be predictable and useful for estimating the individual dose of nedaplatin. Several Phase II studies have suggested that nedaplatin might be a useful second analog, especially for patients with non-small cell lung cancer, esophageal cancer, uterine cervical cancer, head and neck cancer, or urothelial cancer. Further, nedaplatin was reported to be a useful chemotherapeutic agent with radiosensitizing properties; however, there is no Phase III study of nedaplatin, neither with chemotherapy nor with concurrent chemoradiotherapy, because nedaplatin is not commonly used throughout the world. Further evaluation in a randomized controlled trial is warranted to demonstrate definitively the activity of nedaplatin.

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Section: Optimal Dosage Based On Renal Functionsupporting

confidence: 73%

Nedaplatin: a cisplatin derivative in cancer chemotherapy

Shimada¹,

Itamochi²,

Kigawa³

2013

CMAR

Self Cite

104

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Phase I trial of nedaplatin chemotherapy concurrent with radiotherapy for untreated locoregionally advanced nasopharyngeal carcinoma

Liang

Wang

Feng

et al. 2016

Cancer Chemother Pharmacol

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Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

et al. 2013

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Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.

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Area under the curve calculation of nedaplatin dose used in combination chemotherapy with irinotecan in a phase I study of gynecologic malignancies

Abstract: The recommended dosage of NDP calculated by AUC with Ishibashi's formula was set to AUC 10 in combination chemotherapy with CPT-11.

Cited by 5 publications

References 16 publications

Nedaplatin: a cisplatin derivative in cancer chemotherapy

Nedaplatin: a cisplatin derivative in cancer chemotherapy

Phase I trial of nedaplatin chemotherapy concurrent with radiotherapy for untreated locoregionally advanced nasopharyngeal carcinoma

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

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