gastrointestinal tract, thyroid, pituitary gland, liver and skin. Cutaneous adverse events include rash, pruritus, alopecia and vitiligo. A recent study including 1208 patients treated with ipilimumab showed an overall incidence of all-grade rash of 24Á3% 9 with no significant difference of frequency between melanoma and other malignancies, whereas pruritus may affect up to 31% of patients. 10 In the present case, we considered whether the TAD could be attributed to ipilimumab, based upon the following arguments: firstly, the absence of any other chronologically imputable treatment or any cause for abundant sweating; secondly, the complete resolution of the GD almost immediately after ipilimumab disruption, suggesting a direct, toxic (and not immunological) adverse effect and compatible with the ipilimumab half-life of 15 days. We assumed that this rapid clinical improvement was not imputable to the regression of the tumour because the metastatic disease progressed 2 months after the end of the treatment, although the GD did not relapse. Finally, the absence of exacerbation during the infusion period may be explained by the achievement of a stable plasmatic level at the time of the first infusion.To our knowledge, this is the first observation of TAD reported during ipilimumab treatment.

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A chronological homogeneous series of 467 breast cancers has been treated from 1969 to 1974 by tumorectomy followed by irradiation at curative doses: 75 Gy over a period of 7.5 weeks (60 Gy by telecesium and 25 Gy by accelerated electrons). The tumors were exclusively T1 T2/N0 and N1 according to the UICC classification. Symptom-free survival for more than 5 years was achieved in 80% of the cases. Survival was of 88% in the case of T1/N0 tumors and conservation of the breast with a good esthetic result was obtained in 90% (only 2 % invalidating sequelae from radiotherapy). These results could be maintained at 10 years with a survival rate of 77%. In order to achieve maximum security in the supervision of irradiated breast cancers, clinical tests, infrared thermography and radiology should be systematically used. Each method makes approximately 10% of errors, either by excess of by default; combination of these three methods reduces these errors by 4 in either way. One can thus intervene in time in the case of nonsterilized tumors (at about the 10th month) or in the case of a recurrence (at about the 30th month); 60% survival of more than 5 years will then be obtained by surgery.

18088 Background: Pem and CDDP are active agents in many tumor types, and the combination is approved as first line therapy in malignant pleural mesothelioma (meso). Vorinostat (V), an orally active histone deacetylase inhibitor, was shown to induce PR in 2 meso patients (pts) (Krug 2006, Kelly 2005). A Phase I trial was undertaken to determine the safety and maximum tolerated dose (MTD) of Pem+CDDP+V. Methods: Pts with advanced solid malignancies, adequate organ function, ECOG PS = 2, = 1 prior chemotherapy, >18 yrs of age, and at least 6 months from prior treatment with Pem+CDDP were eligible. Patients were treated on 21 day cycles. V was started 2 days before standard doses of CDDP (75 mg/m2) and Pem (500 mg/m2) and was given on 4 schedules: dose levels were: I-200 mg BID for 14/21 d, II- 300 mg BID for 3/7 d wk1, 2 wk rest, III-300 mg QD for 7/21 d, and IV- 400 mg QD for 7/21 d. Results: Twenty-two pts were treated: median age was 60 (range 31–81); 13M: 9F. Tumor types were NSCLC 8, meso 5, bladder 3, colorectal 2, other 4. Nineteen of 22 patients were evaluable for investigator determined response: 1 CR (5.3%), 1 PR (5.3%), 11 SD (57.9%), 6 PD (31.6%). Conclusions: Dehydration and fatigue were common DLTs on different schedules of Pem+CDDP+V. V 300 mg x 7 days was tolerable in this combination. Hints of clinical activity were observed in bladder cancer and sarcoma patients, and stable disease was seen in three mesothelioma patients. Alternative dose schedules of Pem + V are under investigation. [Table: see text] No significant financial relationships to disclose.

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