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Radiotherapy continues to cause skin disorders. In this article, with the aid of our human skin model maintained in ex vivo survival conditions for 15 days, we describe the modifications caused by irradiation and their modulation by a trolamine-containing emulsion (Biafine). Normal human skin fragments were maintained in organ culture. One ionizing radiation session with 5 Gy was applied. Skin parameters were evaluated 24 h after the radiation session and were compared with a nonirradiated skin fragment: vascular modifications (histology), edema, epithelial proliferation, interleukin (IL)-1alpha and IL-6. Another series of skin fragments was maintained in survival conditions for 15 days after the radiation session to evaluate collagen neosynthesis by fibroblasts and any vascular changes (CD34). After irradiation the basal cell proliferation was reduced by approximately 50%. Extensive vasodilation occurred with altered capillary permeability accompanied by decreased CD34 transmembrane protein expression. Collagen synthesis and IL-1 secretion were increased. Biafine significantly reduced capillary alterations, restored CD34 expression as well as epithelial cell proliferation and significantly decreased collagen synthesis and IL-1 expression. With this ex vivo human skin model we confirmed the main modifications induced by radiotherapy as previously described in animal models: decreased basal cell proliferation and endothelial cell alterations and increased collagen synthesis by fibroblasts, probably under the influence of IL-1. The effect of Biafine emulsion on these histological and biochemical parameters may support its clinical efficacy.

Colorectal carcinoma is one of the most common malignancies in the western world, and although fluorouracil (5-FU) has been used in its treatment for almost 40 years, new agents with significant activity have been introduced recently. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, administered at 300 to 350 mg/m2 every 3 weeks is significantly more active than continuous-infusion 5-FU in patients who have experienced disease progression after conventional therapy with 5-FU. In comparison to best supportive care, irinotecan improves survival and preserves quality of life despite treatment-related toxicity. Moreover, the combination of irinotecan and 5-FU has been explored in a number of different schedules. In previously untreated patients, overall response rates are high. Irinotecan can also be combined with mitomycin (mitomycin-C [Mutamycin]), oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum compound that has demonstrated activity against colorectal carcinoma in preclinical trials. It has been evaluated as a single agent against advanced colorectal carcinoma in the salvage setting and also in combination with 5-FU as initial therapy for metastatic disease (where it shows significant activity). The toxicity profile of oxaliplatin (chiefly characterized by neurotoxicity) differs from that of irinotecan (primarily producing diarrhea) and the potential, therefore, exists for combining these agents or for exploiting their possible synergy with 5-FU. The introduction of these two new active agents of different pharmacologic classes promises to enable significant improvements in the treatment of patients with colorectal carcinoma.

Purpose: This article investigates the safety and efficacy of a simple cisplatin-based biochemotherapy regimen, containing single-agent cisplatin plus recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha), in the treatment of metastatic melanoma., Patients and Methods: Between December 1990 and April 1997, 129 patients were treated with cisplatin (100 mg/m2, day 0) plus continuous intravenous infusion rIL-2 (18 MIU/m2/day, days 3-6 and days 17-21) and subcutaneous rIFN-alpha (9 MIU three times per week) plus or minus tamoxifen (160 mg/day) on three different protocols. Tumor response, disease-free survival, and overall survival were evaluated for all evaluable patients (N = 127)., Results: The overall response rate was 49%, and 10% of patients achieved a complete response. Responses were observed at all sites of metastases. In one case, a patient with a large cutaneous inguinal mass experienced a dramatic regression of that lesion within 1 month. The median disease-free survival was 5 months, and median overall survival was 11 months. Patients who responded had a significant survival advantage over nonresponders, and patients who achieved a complete response had a significant survival advantage over patients with a partial response. Toxicities were manageable and reversible upon discontinuation of therapy., Conclusion: The response rates achieved with this simple biochemotherapy regimen are comparable to those for other cisplatin-based biochemotherapy regimens, which use more complex multiagent chemotherapy regimens. We found no added clinical benefit from the addition of tamoxifen to cisplatin.

In this phase I/II study, we assessed the impact of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of advanced ovarian carcinoma combined with the standard regimen cisplatin/cyclophosphamide given as follows: paclitaxel 175 mg/m2 (over 3 hours perfusion with standard premedication), cisplatin 80 mg/m2 (6 to 12 hours after paclitaxel), and cyclophosphamide 400 mg/m2. From February 1994 to January 1996, 27 patients (median age, 55 years; age range, 35 to 74 years) were entered into the study. Eight patients had distant metastases and 19 had early locoregional disease (stage III, 18 patients; stage IC, one patient). Twenty-two patients had undergone prior surgery (simple biopsy, six patients; optimally debulked, nine patients; suboptimally debulked, seven patients). Twenty-one patients had received no prior chemotherapy and six were previously treated with at least one platinum-based regimen. A maximum of six courses of paclitaxel/cisplatin/cyclophosphamide were given every 21 days. Twenty-three patients were evaluable for toxicity: neutropenia (World Health Organization grade 3/4), 91% of patients; thrombopenia (World Health Organization grade 3/4), 13% of patients; two episodes of neutropenia with fever; and neurotoxicity grade 3, 17% of patients. Alopecia grade 3 was reported in all patients. No hypersensitivity reactions and no cardiac toxicity was observed. Among 17 patients evaluable for response (patients with stage IV disease or stage III suboptimally debulked), 12 (70%) clinical complete responses (CRs) and three (18%) partial responses were observed. Among the 12 patients with CRs, 10 underwent second-look laparotomy and seven of them (70%) achieved a pathologic CR. In the group of 11 chemotherapy-naive patients evaluable for response, eight (72%) achieved a CR and three (28%) achieved a partial response. This combination seems to be safe, with very acceptable toxicity, and also seems to be highly active in the treatment of patients with advanced ovarian carcinoma.

Prognosis in metastatic malignant melanoma is poor because of chemo and radiotherapy resistance. However, some drugs, such as dacarbazine, cisplatinum or fotemustine, a new nitrosourea, have produced a response rate of more than 20%. Combining these drugs increases response rate to 30-40%. Immunotherapy by interferon-alpha 2 shows about 15-20% response rate but interleukin-2 would be more effective especially in combination with cisplatinum and interferon-alpha 2 with 50% response and long survival after cessation of treatment.

Conventional imaging (CI) for breast cancer includes mammography and ultrasound. Its limited efficiency is especially manifest for breast cancer follow-up after breast-conserving therapy (i.e. exclusive radiation therapy) and after breast implant. Lack of evidence for definitive diagnosis increases the number of invasive explorations. To improve the specificity of the diagnosis between recurrence or fibrosis, we describe the interest of new imaging (NI) techniques: post-contrast MRI, and MR angiography (MRA), realized in 1 exam. Between October 1993 and December 1994, 82 patients were eligible for these investigations. All patients had an history of conservative breast cancer treatment of breast implant following mastectomy. In all cases CI was not contributive for a precise diagnosis; therefore a biopsy was performed and confirmed the diagnosis of breast cancer. NI was done before biopsy and compared results are following. 19 more patients were evaluated for primary chemotherapeutic response, including a total of 101 patients. Regarding the follow-up of prosthesis and conservative treatment, the correlation with histological control was obtained in 95% with four false diagnoses due to confusion between retroprosthesis relapse and inflammation. Historadiologic correlation were close to 90% for the evaluation of primary chemotherapeutic response. Studies are ongoing to confirm those preliminary findings. Though expansive, these techniques might be cost-effective if they result in a substantial decrease of unnecessary surgical invasive procedures.

64 patients with extra-nodal maxillo-facial NHL were seen between 1969 and 1989. These rare tumours (1 to 4% of stomatological tumours) tended to occur more often in men (60% of cases) between the ages of 40 and 70. Bony involvement was common (maxillary and mandibular involvement), though more rarely the salivary glands or mucosa were involved, presenting as a swelling with lysis of underlying bone. Highly malignant varieties (85% of cases) were most commonly encountered. The treatment remains medical, involving chemotherapy (C.H.O.P. or high dose methotrexate) and gives an actuarial survival rate of 50% at 3 years.