Successful use of dupilumab for the treatment of atopic dermatitis on the genitals, a neglected anatomical site.

Atopic dermatitis (AD) is a chronic inflammatory disease that may involve any cutaneous site; involvement of the genital area may greatly impair patients' quality of life but, as the inspection of genitals is not usually conducted during the routine physical examination of patients with AD, the genital presentation of AD is frequently neglected and under-reported. We decided to evaluate the incidence of genital AD in patients with moderate-severe AD and the relative response to anti-interleukin (IL)-4/IL-13 dupilumab. In our study, a high incidence of genital AD emerged but the use of dupilumab allowed a generalized improvement.

Detection of Polyomavirus in Merkel cell carcinoma by immunohistochemistry: report of three cases.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin, arising from pluripotent precursors of Merkel cells. The tumor most frequently affects head and neck of elderly patients. It increases with sun exposure and after immunosuppression and organ transplantation. Because of a possible viral association, interest in MCC has escalated. A new polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and associated to MCC. In support of this hypothesis, we report three new clinical cases of MCC in which we detected MCPyV by immunohistochemistry and provide an update on current thinking about the MCC.

Purpuric herpes zoster in patients in therapy with clopidogrel.

Clopidogrel is an adenosine diphosphate receptor antagonist used for the prevention of vascular events in patients with atherothrombotic diseases manifested by recent myocardial infarction, ischemic stroke or peripheral arterial disease. Diarrhoea, rash and pruritus are rather common side effects of clopidogrel. Other side effects include epistaxis, nausea, abdominal pain, vomiting, gastritis, gastric and duodenal ulcer. Thrombocytopenia is the most common laboratory abnormality. Leucopenia and neutropenia are rare. We report three cases of purpuric herpes zoster in patients in therapy with clopidogrel. To our knowledge, only one case of haemorrhagic herpes zoster has been published in a patient in therapy with this drug.

Presentation of orf (ecthyma contagiosum) after sheep slaughtering for religious feasts.

We report two cases of orf (ecthyma contagiosum) acquired during religious practices. In the first patient, a 34-year-old Muslim man from Tunisia, orf occurred on the left hand after the patient had handled lamb meat during the "Feast of Sacrifice." In the second patient, a 57-year-old Jewish man, orf was acquired after the "kosherization" of lamb meat and occurred on a finger of the left hand. As approximately 350,000 Muslims reside in the metropolitan area of Milan (Italy), it is possible that in the next future cases of orf acquired after religious practices will occur more often.

Bi-weekly docetaxel and gemcitabine regimen in her-2-negative and anthracycline-pretreated metastatic breast cancer patients: a multicenter phase II trial.

PURPOSE: Bi-weekly gemcitabine (G) in combination with docetaxel (D) is an effective treatment for metastatic breast cancer (MBC) previously treated with adjuvant/neoadjuvant anthracyclines containing regimens with a good toxicity profile. In the present phase II study, we investigated the activity of the same regimen as first-line treatment. METHODS: Women with breast cancer pretreated in adjuvant/neoadjuvant setting with anthracyclines received bi-weekly G (1,250 mg/m² days 1, 15) and D (50 mg/m² days 1, 15) every 28 days with restaging after 3 and 6 cycles. RESULTS: Overall 42 patients were enrolled. Median age is 48 years (range, 31-71 years). Eight patients (19%) achieved complete responses, 18 (43%) partial responses for an overall response rate (ORR) of 62%; five patients (12%) obtained stable disease (SD), and 8 (19%) patients had progressive disease (PD). After a median 17-month follow-up, the median time to disease progression was 12 months (95% CI, 3-26 months) and the median survival time was 27 months (95% CI, 4-57 months). No grade 4 toxicity was seen except in one patient who developed a grade 4 neutropenia. Grade 3 toxicities were leukopenia (2%), neutropenia (14%), anemia (2%), nausea and vomiting (2%), diarrhea (2%), asthenia (2%), and skin toxicity (12%). CONCLUSION: The GD bi-weekly regimen is well tolerated and active as first line in anthracyclines-pretreated women with MBC. It appears as an interesting alternative compared to a 3-week schedule whenever hematological toxicity is the main clinical concern.

A dose finding study of carboplatin and gemcitabine in advanced non-small cell lung cancer.

The excellent activity of the cisplatin-gemcitabine combination and favorable toxicological profile of carboplatin are the basis of carboplatin-gemcitabine combination therapy for non-small cell lung cancer. We carried out a dose-finding study with the aim of establishing the maximum tolerated dose (MTD) of carboplatin on day 1 in combination with gemcitabine at the dose of 1000 mg/m2 on days 1 and 8 in a 21-day cycle. The starting dose level for carboplatin was the area under the concentration time curve (AUC) 4 mg/ml/min. 18 patients were treated and a dose limiting toxicity was observed in 2 cases at the level of AUC 6 mg/ml/min. AUC 5 mg/ml/min was considered as the MTD for carboplatin in our regimen. Notably, 7 objective responses were observed.

Anthracyclines in non-small cell lung cancer.

The literature concerning the use of anthracyclines in the treatment of non-small cell lung cancer (NSCLC) is reviewed here. Overall, the activity of doxorubicin (DOXO) is unsatisfactory, whereas, the analogous epidoxorubicin (EPI) yields a 30% response rate (RR) when administered at intermediate-high doses. All active drugs, including EPI, should be considered to design the most active combination. Mainly, in the setting, in which an objective response is very important, for instance the neo-adjuvant pre-operatory setting.

A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.

We have carried out a pilot study on 25 non-small cell lung cancer patients, administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1 and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg daily. An objective response was observed in 11 cases (44%). The regimen was active, but toxicity was remarkable with some cases of severe myelosuppression and mucositis.

Sequential high dose-density chemotherapy with two active regimens for advanced small cell lung cancer.

16 patients with advanced small cell lung cancer were treated with a combination of cyclophosphamide (1000 mg/m2 day 1), epidoxorubicin (60 mg/m2 day 1) and vincristine (1.4 mg/m2 day 1) every 14 days for six cycles followed by a combination of cisplatin (40 mg/m2 days 1 & 2) and etoposide (100 mg/m2 days 1-3) every 14 days for four cycles. Shortening of intervals was obtained with the prophylactic employment of granulocyte colony-stimulating factor (filgrastim, 300 mcg subcutaneously from day 5 to dsy 10). In 11 patients ratio between actually delivered dose intensity and planned dose intensity of > 80% was obtained. Toxicity was acceptable and no life-threatening toxicities were observed. An objective response (partial or complete) was observed in 11 patients. The new regimen, incorporating the concepts of dose-intensification and sequential administration of regimens, is feasible and may be considered for further studies.

A phase II study of a three-drug combination (cisplatin, ifosfamide and vinorelbine) plus granulocyte-colony stimulating factor in advanced non small cell lung cancer.

Twenty-nine patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of cisplatin 20 mg/m2 days 1-3, ifosfamide 1500 mg/m2 days 1-2 (plus mesna as uroprotector) and vinorelbine 25 mg/m2 days 1 and 5; filgrastim was given at the dose of 300 microg subcutaneously from day 8 to day 15. A response rate of 28% was observed. The activity of this combination in an outpatient setting, with acceptable toxicity, has been demonstrated.

A dose finding study for the combination of epidoxorubicin and vinorelbine, delivered every two weeks with G-CSF support, in advanced breast cancer.

The aim of this study was to find the maximum tolerated dose of epidoxorubicin as part of a regimen with vinorelbine at the dose of 25 mg/m2 on days 1 and 5, every 2 weeks in patients with advanced breast cancer. The optimal dose intensity of the two drugs was supported by administration of granulocyte colony stimulating factor (G-CSF) on days 7-12. Patients were treated with epidoxorubicin at three different dose levels (50-65-80 mg/m2 on day 1 of each cycle). No dose limiting toxicity was observed in the first three patients (treated at the dose of 50 mg/m2). We observed one case of dose limiting toxicity out of the 6 patients treated with 65 mg/m2 and 3/3 cases among patients treated with 80 mg/m2. We conclude that 65 mg/m2 is the maximum tolerated dose of epidoxorubicin in this regimen, which is also able to maintain adequate dose intensities.

A phase II trial of carboplatin, methotrexate and fluorouracil in fluorouracil-pretreated colorectal cancer.

5-Fluorouracil and leucovorin combination is the most commonly applied chemotherapy treatment for colorectal cancer patients, both in the adjuvant setting and for advanced disease. Patients resistant or refractory to the 5-fluorouracil-leucovorin combination have been treated in this phase II trial with carboplatin plus methotrexate and fluorouracil in sequence. Twenty patients with measurable lesions from advanced colorectal cancer were entered in the trial. The treatment plan was carboplatin 300 mg/m2 day 1, methotrexate 40 mg/m2 day 1, fluorouracil 600 mg/m2 day 2, every 21 days. Two patients with liver metastasis had a partial response. Median survival was 12 months (range 4-24). Toxicity was acceptable and no patient had to be hospitalized because of the treatment. In this set of patients activity of the new combination is marginal.

Second line chemotherapy with ifosfamide as outpatient treatment for advanced bladder cancer.

We have carried out a phase II study in advanced or metastatic transitional cell carcinoma of the bladder. Eligible patients had unresectable bladder cancer, previously treated with one line of systemic chemotherapy. Treatment consisted of ifosfamide 1000 mg/sm in a 2-hour infusion for 5 consecutive days from d.1 to d.5. Mesna was administered intravenously at a 20% of the ifosfamide dosage before ifosfamide and orally at 40% after 4 and 8 hours from the ifosfamide infusion. Twenty patients entered the study and received a total of 62 cycles: the treatment resulted feasible on an outpatient basis, with mild toxicity. Only one partial response was observed. With this dose and schedule, ifosfamide appeared less effective than in a previous report at higher doses. Toxicity was acceptable.

Intensified M-VEC chemotherapy with G-CSF support as outpatient treatment for advanced bladder cancer.

The M-VAC regimen (methotrexate, vinblastine, doxorubicin and cisplatin) is widely used in the treatment of advanced or metastatic bladder cancer. In the present trial, an alternate week regimen of M-VEC (with epidoxorubicin instead of doxorubicin) supported by G-CSF (filgrastim) was evaluated. Eligible patients had metastatic or surgically unresectable bladder cancer, not previously treated with systemic chemotherapy. Treatment consisted of methotrexate 30 mg/m2 day 1, vinblastine 3 mg/m2 day 2, epidoxorubicin 60 mg/m2 day 2 and cisplatin 35 mg/m2 days 2 and 3. G-CSF was administered s.c. at the dose of 300 mcg from day 4 to day 11: the treatment was repeated every 2 weeks for six cycles. Twenty-one patients entered the study, and 19 received more than 1 cycle: 78.9% were able to receive full doses of M-VEC as scheduled. The treatment resulted feasible on an outpatient basis, with mild toxicity. Three complete responses (15.8%) and 9 partial responses (47.4%), with an overall objective response rate of 63.2%, were observed.

Phase II study of vinorelbine and ifosfamide in anthracycline resistant metastatic breast cancer.

The new combination of ifosfamide and vinorelbine was evaluated in a phase II study of patients with metastatic breast cancer. All the patients had evaluable or measurable lesions resistant to the combination of cyclophosphamide, epidoxorubicin and 5-fluorouracil. Out of 25 patients entered the trial, 7 achieved an objective response (28%) (95% C.I. 12-49.3). Ten patients (40%) experienced stable disease and the remaining patients (30%) progressive disease. The median time to progression was 4 months (range 2-12+). The activity of the ifosfamide-vinorelbine combination has been demonstrated and the toxicity was acceptable.

A new schedule for etoposide, epidoxorubicin and cisplatin with granulocyte colony stimulating factor for advanced gastric cancer: a feasibility study.

A new polychemotherapy regimen has been developed for gastric cancer. Etoposide at the dose of 120 mg/m2 for three days, Epidoxorubicin at the dose of 30 mg/m2 on day 1 and Cisplatin at the dose of 40 mg/m2 on day 2 were administered to 26 advanced gastric patients every two weeks with the support of Granulocyte Colony Stimulating Factor from day 8 to day 12 of each cycle. The treatment was feasible with most cases (21/25) having received at least four cycles with a dose intensity > 85%, without life-threatening side effects. Toxicity was lower than that observed in the classical combinations of Etoposide-Anthracycline-Cisplatin.