Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: exploratory findings of a case series of 131 stage IV cancers - a retrospective study of a single institution.

The 3-year overall survival (OS) rate of patients with previously treated or untreated stage III or IV melanoma has by now reached 63% using ipilimumab and nivolumab therapy. However, immune-related adverse events (irAEs) of grade 3 or 4 occurred in 59% of patients leading to discontinuation of therapy in 24.5% of patients and one death. Therapy with checkpoint inhibitors could be safer and more effective in combination with hyperthermia and fever inducing therapies. We conducted a retrospective analysis to test the safety and efficacy of a new combination immune therapy in 131 unselected stage IV solid cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Treatment consisted of locoregional- and whole-body hyperthermia, individually dose adapted interleukin 2 (IL-2) combined with low-dose ipilimumab (0.3 mg/kg) plus nivolumab (0.5 mg/kg). The objective response rate (ORR) was 31.3%, progression-free survival (PFS) was 10 months, survival probabilities at 6 months was 86.7% (95% CI, 81.0-92.8%), at 9 months was 73.5% (95% CI, 66.2-81.7%), at 12 months was 66.5% (95% CI, 58.6-75.4%), while at 24 months survival was 36.6% (95% CI:28.2%; 47.3%). irAEs of World Health Organization (WHO) Toxicity Scale grade 1, 2, 3, and 4 were observed in 23.66%, 16.03%, 6.11%, and 2.29% of patients, respectively. Our results suggest that the irAEs profile of the combined treatment is safer than that of the established protocols without compromising efficacy.

Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is an ingredient of chili peppers with inhibitory effects against cancer cells of different origin. We examined the activity of capsaicin on breast cancer cells in vitro and in vivo. The drug potently inhibited growth of ER-positive (MCF-7, T47D, BT-474) and ER-negative (SKBR-3, MDA-MB231) breast cancer cell lines, which was associated with G(0)/G(1) cell-cycle arrest, increased levels of apoptosis and reduced protein expression of human epidermal growth factor receptor (EGFR), HER-2, activated extracellular-regulated kinase (ERK) and cyclin D1. In contrast, cell-cycle regulator p27(KIP1), caspase activity as well as poly-ADP ribose polymerase (PARP) cleavage were increased. Notably, capsaicin blocked breast cancer cell migration in vitro and decreased by 50% the size of MDA-MB231 breast cancer tumors growing orthotopically in immunodeficient mice without noticeable drug side effects. in vivo activation of ERK was clearly decreased, as well as expression of HER-2 and cyclin D1, whereas caspase activity and PARP cleavage products were increased in tumors of drug-treated mice. Besides, capsaicin potently inhibited the development of pre-neoplastic breast lesions by up to 80% without evidence of toxicity. Our data indicate that capsaicin is a novel modulator of the EGFR/HER-2 pathway in both ER-positive and -negative breast cancer cells with a potential role in the treatment and prevention of human breast cancer.

Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis.

BACKGROUND: Oral mucositis is a frequent problem after high-dose methotrexate (HD-MTX), impairing patient's quality of life, leading to higher rates of infections and delaying subsequent chemotherapy. This report describes the effect of palifermin in patients treated within the GMALL-B-ALL 2002 protocol containing HD-MTX who developed a severe mucositis in cycle A1/B1. PATIENTS AND METHODS: Ten patients, all with World Health Organization grades III-IV oral mucositis in cycles A1/B1, obtained palifermin with subsequent similar or identical cycles to reduce mucositis. Thus, patients serve as their own control for efficacy of palifermin. RESULTS: All 10 patients developed grades III-IV mucositis in cycles A1/B1 without palifermin, whereas only two of 10 developed grades III-IV mucositis in corresponding cycles A2/B2 with palifermin. Only four of 10 patients showed infections in the cycles with palifermin compared with 10 of 10 patients without palifermin. The duration of mucositits in patients who acquired a higher grade mucositis despite treatment with palifermin could be reduced from 12.9 days (median) without to 11 days with palifermin. The amount of i.v. opioid analgetics could be significantly reduced. CONCLUSION: Palifermin might reduce the incidence, severeness and duration of oral mucositis in HD-MTX-based chemotherapy and may influence clinical sequelae such as infection and quality of life.

Chemotherapy in metastatic malignant triton tumor: report on two cases.

Malignant triton tumor (MTT) is a rare, highly malignant nerve sheath tumor with rhabdomyoblastic differentiation. Initial debulking surgery followed by adjuvant therapy is the current treatment of choice, but has very limited efficacy when optimal cytoreduction is not achieved by surgical procedure. Neoadjuvant therapy for MTT, to potentially facilitate subsequent surgery, eradicate micrometastatic lesions and, therefore, improve the therapeutical outcome, has never before been presented in literature. Here, we report on the multimodal management of two cases of advanced and metastatic MTT. Treatment modalities involved neoadjuvant and adjuvant chemotherapy, surgical resection, and radiation. In both cases, integrated Positron Emission Tomography/Computed Tomography (PET/CT) emerged as an important diagnostic tool for the reliable assessment of MTT response and metabolic remission.