1135P - Sequential combination of low dose chemo-modulating temozolomide with fotemustine in metastatic melanoma (MM). A phase II study

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anticancer agents
Skin cancers
Biological therapy
Presenter Michele Guida
Authors M. Guida1, A. Cramarossa2, P. Petrillo1, A. Albano1, S. Pisconti3, M. Aieta4, M. Traversa2, R. Ridolfi5, G. Colucci1
  • 1Medical Oncology, National Cancer Research Centre, Bari., 70124 - Bari/IT
  • 2Radiology, National Cancer Research Centre, Bari., 70124 - Bari/IT
  • 3Medical Oncology, Ospedale Civile, Taranto, Italy, 70121 - Taranto/IT
  • 4Medical Oncology, Department of Medical Oncology, National Institute of Cancer, Rionero in Vulture (PZ)., 70122 - Rionero (PZ)/IT
  • 5Medical Oncology, Immunotherapy Unit, National Cancer Institute of Romagna (IRST), Meldola (FC), Italy, 47014 - Meldola (FC)/IT


Background and purpose

MM is a chemoresistant cancer with poor prognosis. Further progress is likely to come from novel targeted antiBRAF therapy, available for about 50% of pts, and from immunotherapeutic agents such as the mAb ipilimumab, at present available only in some countries. Preclinical and clinical experiences support the concept that continuous exposure to an alkilating agent can effectively deplete cells of the DNA repair enzyme O6-methylguanine DNA methyltransferare, the primary mechanism of tumor resistance to chemotherapeutic agents like nitrosurea analogs. Our study was finalized to verify this hypothesis using a sequential combination of low dose chemo-modulating TMZ and FM. Primary endpoints were safety and tumor response evaluation.


53 consecutive MM pts were enrolled in the study. The majority of them (80%) were enrolled before the targeted therapy. The main characteristics included: median age 56 years (21-79); ECOG PS 1 (0–2); number of disease sites: 1 in 30%, 2 in 27%, >2 in 43%; M status: M1a 9%, M1b 21%, M1c 70% with 5 pts having brain metastases. The following schedule was used: oral TMZ 100 mg/m2 d 1 and 2; FM iv 100 mg/m2 d 2, 4 h after TMZ. The regimen was repeated every 3 weeks for a maximum total of 9 cycles. Tumour assessments were conducted at baseline and then every 3 cycles.


52 pts are evaluable for toxicity and 51 for clinical assessment (1 withdrew consent prior to starting treatment; 2 early). The median number of treatment cycles administered was 7 (range 2-9). There were 13 (25%) responses (1 CR and 9 PRs) with a median duration of 7 months, and 12 (23%) stable disease. Median progression-free survival was 6 months and median overall survival 11+ months (range 2-35+ months). Drug-related toxicities ≥ grade 3 included thrombocytopenia (10%), neutropenia (6%), anemia (2%), and hepatopathy (2%). Approximately 75% of pts were treated without dose reduction. Two patients (4%) discontinued therapy because of toxicities.


sequential low dose TMZ and FM demonstrated a high activity in our patient population with an acceptable toxicity. This schedule could therefore represent a good alternative for patients not eligible for targeted therapy or in whom previous targeted therapies failed. The study of the correlation between MGMT level and clinical outcomes is ongoing.


All authors have declared no conflicts of interest.