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Original Article
Quantitative determination of tumor platinum concentration of patients with advanced Breast, lung, prostate, or colorectal cancers undergone platinum‑based chemotherapy ABSTRACT Context: Previous studies have reported direct relationship between tumor reduction and its platinum concentration following platinum‑based (Pt‑based) chemotherapy. However, quantitative data of tumor platinum concentration have not yet been reported for the most common cancers. Aims: Determination of tumor platinum concentration of breast, lung, prostate, and colorectal cancers after Pt‑based chemotherapy; and evaluation of the influence of chemo drug type, chemotherapy regimen, and time lapse from last chemotherapy on tumor platinum concentration. Materials and Methods: Tumor samples of patients with advanced breast, lung, prostate, and colorectal cancers undergone Pt‑based chemotherapy were collected from pathology collection of various hospitals. The platinum concentration of each sample was measured by inductively coupled plasma optical emission spectrometry. The data were categorized by drug type, time lapse from last chemotherapy, and regimen type to evaluate their effects on platinum concentration. Statistical Analysis: ANOVA, Mann–Whitney U and Kruskal–Wallis tests were used. Results: Tumor platinum concentrations of breast, lung, prostate, and colorectal cancers were all obtained in the range of 1–10 µg/g tumor tissue. Large values of P (>0.05) indicate no significant differences between various chemo drug, regimen, and time groups. Conclusions: In general, the platinum concentration was higher in prostate and lower in lung tumors. The type of Pt‑based chemo drug, time lapse from the last chemotherapy, and concurrency of other antineoplastic agents administered with Pt‑based chemo drugs had no significant effect on tumor platinum concentration. KEY WORDS: Breast cancer, colorectal cancer, lung cancer, platinum concentration, prostate cancer
INTRODUCTION According to the World Health Organization, malignant neoplasms are one of the leading causes of death around the world.[1,2] Since the occurrence of cancers increases by population aging, it is predicted that 70% of malignancies occur among people older than 65 years until 2030.[3] The most common and lethal malignancies are lung, colorectal, prostate, and breast cancers.[4] Prostate and breast cancers are the most common and lethal malignancies among men and women, respectively; while colorectal cancer is the second
deadliest after lung cancer in both groups. [5‑7] Platinum‑based (Pt‑based) chemo drugs such as cisplatin, carboplatin, and oxaliplatin are generally the most important candidates for chemotherapy.[8] Cisplatin is used in the treatment of almost 85% of different cancers.[9] Pt‑based chemo drugs are also beneficial to enhance the effect of radiotherapy.[10,11] Nowadays, concurrent chemo‑radiotherapy has This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms.
Hesameddin Mostaghimi1,2, Ali Reza Mehdizadeh1,2, Mohammad Jahanbakhsh1, Amir Reza Dehghanian3, Ramin Askari4 Department of Biomedical Physics and Engineering, School of Medicine, Shiraz University of Medical Sciences, 2 Advanced Health Technologies Research Center, Shiraz University of Medical Sciences, 3Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 4Chemistry Department, Islamic Azad University of Firouzabad, Firouzabad, Iran 1
For correspondence: Dr. Ali Reza Mehdizadeh, Department of Biomedical Physics and Engineering, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Advanced Health Technologies Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. E‑mail: mehdizade@ sums.ac.ir
Access this article online Website: www.cancerjournal.net DOI: 10.4103/jcrt.JCRT_1224_16 PMID: *** Quick Response Code:
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Cite this article as: Mostaghimi H, Mehdizadeh AR, Jahanbakhsh M, Dehghanian AR, Askari R. Quantitative determination of tumor platinum concentration of patients with advanced Breast, lung, prostate, or colorectal cancers undergone platinumbased chemotherapy. J Can Res Ther 2017;13:930-5.
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© 2017 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow
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Mostaghimi, et al.: Tumor platinum concentration
become a common treatment modality superior and more efficient than sequential therapies.[12,13] Due to platinum properties and its definite effects on DNA damage and apoptosis,[14] concurrent chemo‑radiotherapy is performed using mentioned Pt‑based chemo drugs.[15] Some studies have reported the affiliation of antineoplastic effects and tumor platinum accumulation so that more platinum concentration would increase tumor reduction. [16,17] Although multiple statistical studies concerning concurrent chemo‑radiotherapy with Pt‑based chemo drugs have reported positive effects in tumor response and survival rate, [18‑28] quantitative analysis of platinum effects on dose enhancement is not practically possible due to lack of clinical data of platinum concentration;[17,29] while the application of novel methods and drugs (selective local therapy, cisplatin nanocarriers NC6004, multinuclear triplatin BBR3464, and bisplatinum) [30‑32] increases the platinum concentration and the importance of its effect on dose change. Therefore, according to the prevalence of mentioned cancers and chemo drugs, it is essential to determine tumor platinum concentration of patients with advanced breast, lung, prostate, or colorectal cancers undergone Pt‑based chemotherapy. MATERIALS AND METHODS Experimental Tumor samples A total of 0.5 g samples of malignant tumors of patients with breast, lung, or colorectal cancers undergone neoadjuvant Pt‑based chemotherapy with carboplatin, cisplatin, or oxaliplatin in combination with other antineoplastic agents (through trastuzumab, carboplatin (TCH), EP, or m‑FOLFOX regimens) were gathered from pathology collection of various hospitals of Shiraz University of Medical Sciences (SUMS). Compliance with ethical principles related to patient’s rights and privacy, each sample is stored in pathology collection with complete patient records. Prostate tumor samples were collected from patients with metastatic castration‑resistant prostate cancer participated in a pilot study with administration of carboplatin plus docetaxel who had undergone palliative surgery through a transurethral resection of the prostate (TURP). Due to relatively large size of advanced tumors which leads to improbable central blood supply and central necrosis, all samples were resected from tumors external surfaces. Samples were transfered to laboratory of analysis and identification of chemical elements of Shiraz University, and platinum concentrations were measured by standard method of measuring heavy metals in living organs.[33‑35] Breast Breast cancer samples were related to some selected patients with locally advanced malignancies who had become operable following neoadjuvant carboplatin‑based chemotherapy. Among 16 samples, 10, 5, and 1 samples were related to patients of Stages IIIA (T3N1M0), IIIB, and inflammatory, respectively. All patients were human epidermal growth
factor receptor 2-positive (HER2- positive) who had undergone mastectomy and specific chemotherapy regimen of TCH plus pertuzumab. Among patients, one case had undergone surgery
