Radiation Therapy and Concurrent Cisplatin Administration in Locally Advanced Head and Neck Cancer a Hellenic Co-Operative Oncology Group Study

In an attempt to improve local control of locally advanced head and neck cancer, radiation therapy was combined with cisplatin. Forty-eight patients entered into this study. All patients were irradiated with a ⁶⁰Co unit and according to the protocol they should receive 70 Gy in the tumor area and 45 Gy in the rest of neck. Cisplatin was administered at a dose of 100 mg/m² on days 2, 22 and 42. Thirty-seven (80%) patients received the total radiation dose as initially planned. Thirty-four (72%) patients achieved complete and 5 (10%) partial response. Grade 3-4 toxicities included vomiting (14%), stomatitis (4%), diarrhea (2%), myelotoxicity (14%), hoarseness (4%), dysphagia (30%), weight loss (32%), nephrotoxicity (4%) and dermatitis (2%). After a median follow-up of 26 (range, 18-33) months, 16 patients have died. Among the 35 complete responders 6 later on relapsed. Median relapse-free survival has not yet been reached. Combined radiation therapy and cisplatin appears to be a highly active treatment in patients with advanced head and neck cancer as far as primary locoregional response is concerned.     

Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

Summary Purpose To assess the prognostic and predictive significance of HER-2 overexpression and high expression of VEGF in high-risk patients with breast cancer treated with dose–dense sequential chemotherapy. Patients and methods From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m² followed by three cycles of paclitaxel (T) 250 mg/m² followed by three cycles of “intensified” CMF (cyclophosphamide 840 mg/m², methotrexate 47 mg/m² and fluorouracil 840 mg/m²) or to four cycles of E, followed by four cycles of CMF. HER-2 was assessed by immunohistochemistry (IHC) in 394 patients, and by fluorescence in situ hybridization (FISH) in cases scored as 2+ by IHC. VEGF was evaluated in 323 patients by IHC. Results HER-2 overexpression was detected in 123 patients (31%) and high expression of VEGF in 233 (72%). The rate of HER-2 overexpression was significantly higher in patients with positive VEGF staining (35% vs. 21%, p=0.02). Overexpression of HER-2 was significantly associated with negative hormonal status, high histologic grade and larger tumors. HER-2 overexpression was a significant negative predictor of DFS (p=0.002), but not of OS. Adjusting for HER-2 overexpression, DFS and OS did not significantly differ between treatment groups. Positive VEGF staining was not associated with receptor status, number of positive nodes, grade, tumor size, incidence of relapse or death. Conclusions For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.     

Paclitaxel and gemcitabine, as first-line chemotherapy, combined with trastuzumab in patients with advanced breast cancer: a phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG)

Purpose: Advanced breast cancer (ABC) is an incurable disease. Standard first-line treatment for patients with HER-2/neu overexpressing tumors includes the combination of the humanized monoclonal antibody trastuzumab with chemotherapy, mainly paclitaxel. This combination is the first to demonstrate a survival advantage in this group of patients. To improve on these results, we investigated a triplet, paclitaxel-gemcitabine-trastuzumab (TGH), in a phase II study. Patients and Methods: Patients with ABC were accrued to the study. Treatment consisted of paclitaxel 80 mg/m²/week, gemcitabine 1000 mg/m² every 2 weeks, and trastuzumab 4 mg/kg loading dose and then 2 mg/kg/week. Patients were treated on study for a total of 12 weeks. Response evaluation was performed at the end of the 12 weeks. Continuation of treatment beyond the 12 weeks was left to the discretion of the investigator. Primary study endpoint was response. Toxicity assessment and survival were secondary endpoints. Results: Between November 2000 and May 2002, 40 patients were accrued and 32 patients completed all 12 weeks of therapy. One patient died of septic shock during therapy. Grade III and IV neutropenia was seen in 12.5% of cases each. Grade III anemia was seen in two patients, and grade III and IV thrombocytopenia in three and two patients, respectively. Both paclitaxel and gemcitabine were delivered at 86% of the planned dose intensity. Six patients achieved a complete response (CR) and 15 a partial response for an overall response rate of 52.5%. An additional 25% demonstrated stable disease and 20% progressive disease. Median duration of response was 14 months. All six patients who achieved CR are still in CR for 6 to 19 months. After a median follow up of 12.2 months, 19 patients have progressed and 7 have died. Median time to progression is 13.7 months, whereas median survival has not been reached. Conclusion: TGH is a well-tolerated and effective regimen for the first-line treatment of ABC. Randomized comparison between paclitaxel, trastuzumab, and triplets are warranted.     

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study

PURPOSE: To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin (CDDP) in terms of response rate, time to progression (TTP) and overall survival (OS), as well as the tolerability of the regimen in patients with brain metastases from solid tumors. PATIENTS AND METHODS: Patients (n=32) with brain metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200 mg/m2/day (chemotherapy-naive) for 5 days, combined with CDDP 75 mg/m2 on day 1, every 28 days. Primary tumor sites included breast cancer (n=15), lung cancer (n=12) and other (n=5). Twenty-seven patients had received prior chemotherapy for extracranial disease and 17 had prior radiotherapy to the brain. RESULTS: One patient (3.1%) with non-small cell lung cancer (NSCLC) achieved complete response. Nine patients (28.1%; six with breast cancer, two with melanoma and one with NSCLC) achieved a partial response and five patients (16%) had stable disease. Median OS was 5.5 months and median TTP 2.9 months. One patient died from septicemia/neutropenic fever. Grade III-IV toxicities included anemia (9%), leukopenia (6%), thrombocytopenia (3%), renal toxicity (3%), headache (3%), fatigue (3%), nausea (3%), vomiting (3%), and alopecia (6%). CONCLUSIONS: TMZ combined with CDDP is an active and well-tolerated combination in patients with brain metastases from solid tumors.     

Beneficial effect of nerve growth factor-7S on peripheral nerve regeneration through inside-out vein grafts: an experimental study

This study investigated the effect of local administration of nerve growth factor-7S (NGF-7S) on the axonal regrowth of mixed peripheral nerves through inside-out vein grafts. Sixty male Wistar rats were randomized into two groups (n = 30). A defect 12 mm long in the right sciatic nerve was created and repaired with an inside-out vein graft from the right jugular vein. NGF-7S (group A) or phosphate-buffered saline (group B; control) was locally administered daily during the first 3 weeks. Walking-track analysis and electrophysiological and histological-morphometric studies were carried out 4, 6, 8, 10, and 12 weeks postoperatively (subgroups a, b, c, d, and e, respectively, n = 6 each). Data analysis showed that 1) the recovery of motor function, as measured by walk pattern analysis and evoked muscle action potential, and 2) the orientation, number, myelin thickness, and diameter of myelinated fibers were better in the NGF-7S than in the control group. These findings present strong evidence of the beneficial effect of NGF-7S on peripheral nerve regeneration through inside-out vein grafts.     

Prefabricated hair-bearing temporal flap for two different facial aesthetic subunits reconstruction: case report

Expanded temporal hair-bearing scalp as a pedicled flap was used to reconstruct the upper lip with a moustache and also the ipsilateral eyebrow, on a patient with an old chemical burn of the face. It is a relatively simple method of providing cover of the upper lip and eyebrow with a good density of hair and a natural hair flow. The results were satisfactory and the donor site morbidity was minimal.     

Combination docetaxel (Taxotere), fluorouracil, and leucovorin (TFL), as first-line chemotherapy in advanced gastric cancer: a Hellenic Cooperative Oncology Group phase II study

Background We assessed the efficacy and safety profile of a docetaxel (Taxotere; Sanofi-Aventis, France), fluorouracil (FU), and leucovorin (LV) combination (TFL), as first-line chemotherapy in patients with advanced gastric cancer. Methods Fifty-eight patients with advanced gastric cancer were entered in this phase II study. The chemotherapy regimen (TFL) was administered in an outpatient setting as follows: docetaxel 7mg/m² on day 1 and FU 50mg/m² and LV 30mg/m² on days 1 to 3, every 3 weeks for six cycles. Results On an intent-to-treat basis, 4 complete (7%) and 11 partial responses (19%) were observed, with an objective overall response rate of 26%; in addition, 22 patients (38%) had stable and 15 (26%) had progressive disease. For 6 (10%) patients, response could not be evaluated. Responses were noted at all metastatic sites. With a median follow-up of 55 months, median survival was 9 months; median time to progression, 5.9 months; and median duration of response, 10 months. Toxicity was manageable and no toxic death was reported. Neutropenia was the most frequent severe toxicity and occurred in 30% of the patients. The main non-hematologic toxicities were alopecia (76%), diarrhea (30%), and stomatitis (30%). Conclusion The results of this phase II study seem to indicate that the TFL regimen has moderate activity in patients with advanced gastric cancer, with acceptable toxicity.     

Intranasal complications in women with osteoporosis under treatment with nasal calcitonin spray: case reports and review of the literature

OBJECTIVE: To describe the nasal side effects of postmenopausal women suffering from osteoporosis and being treated with intranasal calcitonine (InC). METHOD: Two women who presented with nasal complaints, were diagnosed as having nasal septum perforation and septum-concha inferior synechiae respectively. Both were receiving treatment with InC for postmenopausal osteoporosis. A medline search for similar side effects of InC revealed a range of nasal symptoms and several factors that could induce these symptoms. RESULTS: Exclusion of other causative conditions leads us to attribute the nasal findings to the use of InC. The literature mentions mild and usually reversible side effects from use of InC. Substances included in the calcitonine spray (preservatives, accelerators of absorption), the development of antibodies against the hormone and possible implication of coexisting diseases or medications to the provocation of nasal side effects, are discussed. CONCLUSIONS: Intranasal administration of calcitonine is an established therapy for postmenopausal osteoporosis and other skeletal diseases. The side effects from its use are commonly local, mild and transient, but there is not sufficient information on how this process begins. An ENT examination before and during therapy with InC would be beneficial to patients for the recognition and prevention of serious side effects.     

Risk associations of melanoma in a Southern European population: results of a case/control study

OBJECTIVES: Limited data exist about the risk factors of melanoma in the Greek population. We investigated the association of melanoma with phenotypic and solar indices in this darker skin population residing in an environment of high ambient ultraviolet radiation. METHODS: Our study included 200 sporadic melanoma cases and 200 age-, sex-matched control subjects. Information on history of sun exposure patterns and cutaneous reaction to sunlight was obtained and a clinical evaluation of pigmentary traits, pigmented lesions, and actinic keratoses was performed. RESULTS: In the multivariate analysis, fair skin (OR: 4.63, for fair skin versus light brown, 95% CI: 1.54-13.92), intermittent sun exposure during childhood (OR: 3.33, >2 weeks/year of sun exposure versus /=10 nevi versus no nevi, 95% CI: 1.65-23.76) and the presence of clinically atypical nevi (OR: 2.84, 95% CI: 1.16-6.98), solar lentigenes were an independent risk factor of melanoma (OR: 4.33, 95% CI: 1.67-11.22). CONCLUSIONS: Intermittent sun exposure of moderate intensity during childhood/adolescence and outdoor leisural activities, in conjunction with a more resistant skin phenotype to acute sunburns and a strong association with nevi and solar lentigenes was a prominent determinant of melanoma risk in our population.     

Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population

Individuals with melanocortin 1 receptor (MC1R) gene variants have been shown to carry an increased risk for the development of melanoma. In this study, we investigated the relationship of MC1R gene variants and the risk of melanoma in 123 melanoma patients and 155 control subjects from Greece. The entire MC1R gene was sequenced for polymorphisms and the results were correlated with host factors and pigmentary characteristics. MC1R polymorphisms were present in 59.4% of melanoma patients compared to 37.5% of controls, yielding an odds ratio (OR) of 2.43 (95% confidence interval (CI) = 1.50-3.96, P < 0.001) for melanoma among MC1R carriers. The risk of melanoma was enhanced in individuals carrying multiple variant alleles (OR = 6.97; 95% CI = 1.86-26.12, P = 0.004). Only the Val60Leu, Arg142His, and Arg151Cys variants were significantly associated with melanoma risk. In stratified analysis, the risk of melanoma among MC1R carriers was not influenced by skin phototype, skin color, or hair color. No association was found between MC1R genotype and the age of onset of melanoma, the tumor location, or the tumor thickness. In conclusion, MC1R polymorphisms are a predisposing factor of melanoma in a southern European population with a relatively low incidence of the disease.