The First American Cancer Patient to Receive Dicycloplatin Chemotherapy: a Case Report
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Journal of Cancer Research & Therapy An Open Access Publisher Yu JJ et al., J Cancer Res Ther. 2017, 5(9):56-60 http://dx.doi.org/10.14312/2052-4994.2017-11 Case report Open Access The first American cancer patient to receive dicycloplatin chemotherapy: A case report Jing Jie Yu1,*, Mohamad W. Salkini2, Shunchang Jiao3, Thomas Hogan4, Yi Guo1, Xiaobing Liang1, Bo Yang3, Li Zhang3 and Kymberly Gyure5 1 West Virginia University Cancer Institute, School of Medicine and School of Pharmacy, West Virginia University, Morgantown, WV, USA 2 Department of Surgery/Urology, School of Medicine, West Virginia University, Morgantown, WV, USA 3 Oncology Department of Internal Medicine, PLA Hospital, Beijing, China 4 Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV, USA 5 Department of Pathology, School of Medicine, West Virginia University, Morgantown, WV, USA Abstract Dicycloplatin (DCP), an effective platinum drug, was developed in China and approved by Chinese FDA in 2012. Its side effects are more bearable than those of cisplatin and carboplatin. The bladder cancer patient presented here was a 65-year-old Caucasian American male diagnosed at West Virginia University (WVU) Hospital in the USA and received 8 weeks of dicycloplatin chemotherapy in Beijing in 2016. He experienced moderate fatigue and aches but no vomiting or hair loss. His blood values decreased but remained in normal range. Quarterly cystoscopic follow-ups at WVU Hospital found no tumor recurrence. Studies of dicycloplatin-induced activation of the molecular signaling pathway in response to DNA damage, including investigation of Chk2, BRCA1 and p53, demonstrated that the signaling pathway is activated only in cancer cells, not in normal cells. Other in vitro data also indicate DCP mainly affects tumor cells, largely bypassing normal cells. These findings may explain DCP's more bearable side effects. Dicycloplatin may offer chemotherapeutic advantages over some platinum drugs in cancer treatment. Keywords: dicycloplatin; chemotherapy; bearable side effects; bladder cancer; molecular mechanism pathway Introduction development of dicycloplatin (DCP). DCP is a non-covalent association of complexes or molecules (a supramolecule) Cancer is one of the leading causes of morbidity and assembled through four strategically-placed hydrogen mortality worldwide, with approximately 14.1 million new bonds. Clinical observations show that DCP possesses cases in 2012; of these 7.4 million cases were in men and superior anticancer efficacy through its broad-spectrum 6.7 million in women [1]. The annual number of new cases effects, high antineoplastic activity, low toxicity, and good is expected to increase to 24 million by 2035 [2]. tissue penetration [4-6]. The rate of cancer death in the United States for men and DCP for intravesical injection was developed for a Chinese women combined fell 25% from its peak in 1991 to 2014. phase I human clinical trial completed in 2006. From 2007 This decline translates to the prevention of millions of to 2009 a double-blind, randomized multicenter phase cancer deaths [3]. That is significant progress; however, II clinical trial comparing dicycloplatin and paclitaxel to 1,685,210 new cancer cases and 595,690 cancer deaths are carboplatin and paclitaxel in non-small cell lung cancer projected in the USA in 2016 [3]. Platinum-containing antineoplastic agents remain a Corresponding author: Jing Jie Yu, MD, WVU Cancer Institute, School of Medicine and School of Pharmacy, West Virginia University, Morgantown, cornerstone of chemotherapy for many cancers, including WV, USA. Tel.: 304-293-8661; Email: [email protected] bladder cancer. The primary platinum drugs are cisplatin Received 15 July 2017 Revised 29 September 2017 Accepted 4 October 2017 and carboplatin. Unfortunately, the side effects of these Published 10 October 2017 drugs are often severe, causing some patients to stop Citation: Yu JJ, Salkini MW, Jiao S, Hogan T, Guo Y, Liang X, Yang B, Zhang treatment. Toxic effects include myelosuppression, L, Gyure K. The first American cancer patient to receive dicycloplatin nephrotoxicity, hepatotoxicity, neurotoxicity, ototoxicity, chemotherapy: A case report. J Cancer Res Ther. 2017; 5(9):56-60. DOI: and nausea and vomiting. These are often constraints to 10.14312/2052-4994.2017-11 giving full dosage and to long-term use. Copyright: © 2017 Yu JJ, et al. Published by NobleResearch Publishers. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution The need for highly-potent platinum anticancer drugs with and reproduction in any medium, provided the original author and source low toxicity and broad-spectrum effectiveness led to the are credited. 57 Yu JJ et al., J Cancer Res Ther. 2017, 5(9):56-60 was completed (NSCLC) [7, 8]. Two hundred and forty all visible bladder tumor with adequate depth to include chemotherapy-naïve patients with advanced NSCLC were the muscularis propria [18]. To prevent recurrence of recruited from 15 multi-center/hospitals in China. The non-muscle invasive tumors (T1, Ta), resection is typically study concluded that DCP was not inferior to carboplatin followed by intravesical treatment if the tumor was high- in efficacy or toxicity. In March 2012, dicycloplatin injection grade urothelial carcinoma or in the event of large tumors was approved for chemotherapy by the Chinese FDA or multifocal disease. BCG is the most commonly used [4-6]. agent for intravesical therapy. It is the standard protocol. Other intravesical agents have been compared with BCG Bladder cancer (BC) caused 170,000 deaths annually but most are inferior and none consistently proven to be worldwide. It is the 4th most common cancer in men and superior [19-23]. the 9th in women in the United States. More than 50,000 men and 16,000 women are diagnosed with BC each year Case report in the US [9, 10]. Bladder cancer arises from the epithelial A 65-year-old Caucasian American male with increasing lining of the urinary bladder. The most common type is hematuria over a 4-month period, without lower urinary transitional cell or urothelial cell carcinoma, which can also tract symptoms, was seen in June of 2016 at West Virginia arise in the histologically similar urothelium of the renal University (WVU) Hospital, Morgantown, WV, USA. The pelvis or ureters. patient was a former smoker. The work up, with CT- Urography and cystoscopy, showed a 1.5 cm bladder BC commonly presents with hematuria -- visible mass. Transurethral resection was performed on June (macroscopic) or microscopic -- noted in 80-90% of patients. 30, 2016. The pathologic diagnosis was non-invasive high- It may also present with painful urination, increased grade papillary urothelial carcinoma involving the right frequency of urination, or urgency. Advanced BC may be lateral wall bladder tumor (Ta) (Figure 1). Immunotherapy accompanied by pelvic, flank, or bone pain, leg edema or with BCG and surveillance cystoscopy were recommended a palpable pelvic mass on physical examination. Tobacco to the patient. The patient declined BCG treatment course smoking is associated with over half of the cases in men but elected cystoscopic surveillance every three months at and one-third in women [11, 12], with an almost linear WVU after dicycloplatin chemotherapy in Beijing, China. relationship between smoking duration (in years), pack per years, and BC risk. Although quitting smoking lowers the risk, former smokers are likely always at a higher risk of BC versus never smokers [13]. The standard diagnosis for bladder cancer is cystoscopic biopsy. Transurethral resection of bladder tumor (TURBT) during cystoscopy and bimanual examination done pre- and post-TURBT can help assess whether the tumor is fixed ("tethered") to the pelvic wall. The pathological classification obtained at TURBT is of fundamental importance in choosing treatment and/or follow-up routines [14]. BC treatment depends on depth of tumor invasion. Non- muscle invasive tumors can be removed by transurethral resection of bladder tumor and serve primarily for pathological staging [14]. Intravesical immunotherapy with Bacillus Calmette–Guérin (BCG) is typically used to treat Figure 1 Sections demonstrate a non-invasive, high-grade urothelial and to prevent recurrence of non-muscle invasive tumors carcinoma. The tumor is composed of urothelial mucosa of increased thickness resting on fibrovascular cores. There is focally prominent nuclear [15] and in randomized trials is superior to standard atypia. (Hematoxylin-eosin, original magnification 200X). chemotherapy [16]. However, the rate of recurrence after adjuvant BCG treatment in bladder cancer is about 50% Of note, the patient is a former smoker. His mother died (90% without BCG). Untreated, non-muscle invasive tumors of ovarian cancer at age 50 and his father had advanced may gradually infiltrate the muscular wall of the bladder, prostate cancer at the time of his death at age 81 from other requiring cystectomy and urinary diversion into an isolated causes. The patient’s family history and his familiarity with bowel loop (an ileal conduit or urostomy) or a substitute DCP through his work as a medical writer led him to elect bladder (neobladder) from a segment of intestinal tissue. DCP. In July 2016, the patient traveled to Beijing where he For muscle invasive BC, the gold standard is cystectomy received eight weekly DCP IV infusions. (partial or radical cystectomy depending on tumor