Department of Dermatologic Oncology
Naoya Yamazaki, Arata Tsutsumida, Akira Takahashi, Kenjiro Namikawa, Wataru Omata
The Department of Dermatologic Oncology has consistently served as the core hospital to establish treatment strategies for malignant skin tumors since the National Cancer Center opened in 1962, with over 2000 cases of malignant melanoma treated to date; an impressive number for a hospital or research institution in Japan. Today, patients are referred here from all over Japan. Particularly noteworthy is the total of 181 patients with malignant melanoma, approximately double the number of five years ago. Most of the patients are examined and treated for skin cancer, including malignant melanoma. Surgery is the main treatment modality for skin cancer, while multidisciplinary treatments, comprising chemotherapy, immunotherapy and radiotherapy, are also routinely carried out. This Department is also actively involved in multicenter trials for new skin cancer agents all over Japan.
The Department has four staff dermatologic oncologists, one chief resident and three residents. We also engage in routine outpatient activities on Wednesdays and Thursdays in the National Cancer Center East.
Our Department has a high throughput, with an average of more than 200 patients with malignant melanoma seen annually for the past four years. This follows the establishment of a national network to develop treatment for malignant skin tumors, thanks to which nivolumab, an anti-PD-1 antibody, was approved as a therapeutic agent for malignant melanoma in Japan as a world first and reflecting vigorous new drug development.
An expanded access program featuring a BRAF inhibitor, vemurafenib, was also conducted through an investigator-initiated clinical trial.
About 20 patients are hospitalized to undergo surgery, chemotherapy, or radiation therapy. In 2013, 250 operations were performed, including 118 under general anesthesia. Rounds are made and case presentations are held every morning. A Division conference is also held every Monday to discuss the therapeutic principles for outpatients and inpatients. A clinicopathological conference focusing on surgically removed skin specimens is held with pathologists once a month.
We have also treated patients with advanced cases of mucosal melanoma in the nasal cavity, genital lesions, perianal lesions and uveal melanoma, despite our original “dermatologic” specialty.
Malignant skin tumors are mainly treated by surgery (appended table). However, in recent years, several new drugs have been rapidly developed overseas to treat malignant melanoma and our Department has been conducting numerous clinical studies and trials, with the most important listed as follows:
- A multicenter study to establish standard therapy for refractory malignancies
- A study on the establishment of an early clinical development system of drugs for rare cancers and support for research.
- Development of a system for boron neutron capture therapy (BNCT) using an accelerator installed at the hospital
- A study for developing guidelines to support the physical appearance of cancer patients
- A study on methods for assessing skin changes associated with cancer treatment and establishment of standard care
- A study on the quantitative assessment of skin disorders associated with chemotherapy using molecular-targeted agents and skin care
- A retrospective study to clarify the outcomes of conventional treatment for cutaneous angiosarcoma of the head and neck
- A retrospective study on the outcomes of TACE therapy using cisplatin for liver metastasis from primary ocular malignant melanoma
- A phase I/II trial of combined dabrafenib and trametinib in patients with BRAF V600E or V600K mutation-positive advanced solid cancer (for phase I trials) or cutaneous malignant melanoma (for phase II trials)
- A randomized double-blind Phase III study comparing placebo and combination therapy with dabrafenib (GSK2118436) and trametinib (GSK1120212), given as postoperative adjuvant therapy for BRAF V600 mutation-positive malignant melanoma (a group at high risk of recurrence)
- A phase II, open-label, multicenter study to evaluate the efficacy and safety of avelumab (MSB0010718C) in patients with Merkel cell carcinoma
- A phase I study of repeated intratumor administration of TBI-1401 (HF10) in patients with solid tumors with superficial lesions
- A working group to prepare guidelines on “Antiimmune checkpoint therapy and combination therapy” or leaflets explaining the guidelines
- “Development of innovative cancer immunotherapy by identifying essential aspects of the tumor microenvironment associated with malignant melanoma”
- Clinical evaluation of a practical, non-invasive diagnostic tool for superficial skin tumors (hyperspectral imager)
- Practical development of therapeutic agents for refractory skin cancer using innovative molecular-targeted agents inducing cancerspecific apoptosis through an investigatorinitiated clinical trial
Table2 shows our clinical trials.
Currently, three resident physicians and one oncology trainee are engaged in ongoing training in routine clinical practice under skilled guidance. Conferences with the Departments of Oncology, Radiotherapy and Pathology are also regularly held. The resident physicians and the oncology trainee made a total of ten presentations at domestic academic conferences and one presentation at an international academic conference as well as publishing two papers.
We have devised certain measures to resolve the drug lag between Japan and Western countries in the treatment of malignant melanomas and will further promote efforts to develop effective and safe treatment strategies.
Our Department is a high-volume center in Japan for malignant melanomas and other malignant skin tumors. With the advantageous data collection associated with such a large patient base, we will reinforce our research collaboration system even more than at present, leveraging a translational research platform with the National Cancer Center Research Institute.
List of papers published in 2015
- Yamazaki N, Kiyohara Y, Sugaya N, Uhara H. Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAF(V) (600) mutations. J Dermatol, 42:661-666, 2015
- Yamazaki N, Tanaka R, Tsutsumida A, Namikawa K, Eguchi H, Omata W, Oashi K, Ogawa T, Hayashi A, Nakamura N, Tsuta K. BRAF V600 mutations and pathological features in Japanese melanoma patients. Melanoma Res, 25:9-14, 2015
- Yamazaki N, Kiyohara Y, Uhara H, Fukushima S, Uchi H, Shibagaki N, Tsutsumida A, Yoshikawa S, Okuyama R, Ito Y, Tokudome T. Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma. Cancer Chemother Pharmacol, 76:997-1004, 2015
- Yamazaki N, Uhara H, Fukushima S, Uchi H, Shibagaki N, Kiyohara Y, Tsutsumida A, Namikawa K, Okuyama R, Otsuka Y, Tokudome T. Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma. Cancer Chemother Pharmacol, 76:969-975, 2015
- Sakaizawa K, Ashida A, Uchiyama A, Ito T, Fujisawa Y, Ogata D, Matsushita S, Fujii K, Fukushima S, Shibayama Y, Hatta N, Takenouchi T, Uehara J, Okuyama R, Yamazaki N, Uhara H. Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. J Dermatol Sci, 80:33-37, 2015
- Nakamura Y, Ohara K, Kishi A, Teramoto Y, Sato S, Fujisawa Y, Fujimoto M, Otsuka F, Hayashi N, Yamazaki N, Yamamoto A. Effects of non-amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma. J Dermatol, 42:861-866, 2015
- Sato S, Nakamura Y, Shimizu M, Yamada K, Teramoto Y, Yamazaki N, Yamamoto A. Giant pedunculated pilomatrix carcinoma on the upper limb: A rare clinical appearance. Eur J Dermatol, 25:91-92, 2015
- Nakamichi S, Nokihara H, Yamamoto N, Yamada Y, Fujiwara Y, Tamura Y, Wakui H, Honda K, Mizugaki H, Kitazono S, Tanabe Y, Asahina H, Yamazaki N, Suzuki S, Matsuoka M, Ogita Y, Tamura T. Phase I and pharmacokinetics/pharmacodynamics study of the MEK inhibitor RO4987655 in Japanese patients with advanced solid tumors. Invest New Drugs, 33:641-651, 2015