Nicolas Mylonakis

Combination chemotherapy with cisplatin-vinblastine in malignant mesothelioma

From June 1985 to March 1993, 20 consecutive patients with histologically proven malignant mesothelioma were treated with cisplatin 100 mg/m2 i.v. infusion on day 1 and vinblastine 6 mg/m2 i.v. on day 1 and 8. Treatment was repeated every 4 weeks until progression. All patients were evaluated clinically and by CT-scan and were staged (Stage IV), according to Butchards criteria, on entry to the study. None had prior surgical excision. Eighty-one chemotherapy cycles were administered to 20 patients. One complete response, four partial responses, nine stable diseases and six progressions were noted. One partial responder entered complete response following an operation. Toxicity was acceptable and no treatment-related deaths occurred. The median survival for responders was 19.3 months; for patients with stable disease 15.7 months and for non-responders, 5.2 months. The mean duration of response was 13 months. We conclude that for this small group of patients, the combination cisplatin-vinblastine is effective, with acceptable toxicity in malignant mesothelioma. Further study with a larger number of patients is necessary.

Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer

The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with clinical outcome under treatment. CSF tumor marker levels correlated with response to treatment and outcome in each patient, and, despite achieving negative CSF cytology after therapy in two patients, it heralded disease progression. Given our findings, CSF tumor marker evaluation may provide a reliable means and surrogate end-points of monitoring response of carcinomatous meningitis to treatment. Therefore, large studies to assess the value of CSF tumor marker changes in carcinomatous meningitis are warranted.

Comparison of ondansentron (GR 38032F) versus ondansentron plus alprazolam as antiemetic prophylaxis during cisplatin-containing chemotherapy.

The purpose of our study was to evaluate the effectiveness of alprazolam (APZ) as an adjuvant drug to ondasentron against cisplatin-induced emesis. All patients received CDDP 100 mg/m2, and had previously received chemotherapy. We established two groups of patients randomly: Group A patients received 5-HT, alone, and Group B received 5-HT3 and APZ. The drugs were administered as follows: 5-HT3 was given at a dose of 1 ampule 8 mg in 100 ml N/S in 10 minutes IV infusion before the infusion of CDDP. We continued with 1 tablet 8 mg in the afternoon and 1 before sleeping the first day; for the next two days, patients received 3 tablets 8 mg/day. APZ was given in tablets of 0.25 mg 60 minutes before CDDP infusion and then with the second and third dose of 5-HT3. We did not find significant differences in clinical parameters and factors, especially anxiety, that influenced vomiting between the examined groups. The mean number of vomiting episodes without gastric content (4.76 episodes) and the mean duration of nausea (195 minutes), were greater in Group A than in Group B (1.39 episodes. p < .0001; 91 minutes, p < .049). Differences also were found in the mean number of vomiting episodes with gastric content between the examined groups (A: 1.97; B: 1.09; p < .135). The intense of nausea and vomiting according to WHO classification was greater in Group A (grade 0, p < .004; grade 2, p < .020) than in Group B. Patients of Group B had fewer problems with appetite (p < .027), and more intense sedative effect (grade 0 [p < .001], 1 [0.027], 2 [0.022]) than patients of Group A. In conclusion APZ improved the antiemetic efficacy of ondasentron in cisplatin-induced emesis.

Diphenhydramine for nausea and vomiting related to cancer chemotherapy with cisplatin

Abstract High dose metoclopramide and adjuvant drugs, such as corticosteroids, benzodiazepines, and drugs with antidopaminergic, anticholinergic, or antihistaminic effects, are the most widely used antiemetics in cancer patients receiving chemotherapy, particularly cisdichloro-diammine platinum II (cisplatin). The purpose of our prospective randomized study was to investigate the possible antiemetic efficacy of diphenhydramine as an adjuvant antiemetic drug when combined with metoclopramide (MCP). A total of 91 patients were assigned to either group A ( N = 44) who received only MCP and group B ( N = 47) who received the combination of MCP and diphenhydramine. All patients received cisplatin-based combination chemotherapy for the first time and were evaluated only once in order to exclude the effects of anticipatory nausea and vomiting. There were no statistically significant differences between the two groups except that patients treated with diphenhydramine presented more sedative effects and had more limited activity. Also diphenhydramine did not give absolute protection from the extrapyromidal side effects of MCP. Side effects of diphenhydramine were minimal and well tolerated. We conclude that diphenhydramine is not a useful adjuvant drug in the antiemetic therapy.

Ondansetron Versus Metoclopramide as Antiemetic Treatment During Cisplatin-based Chemotherapy: A prospective study with special regard to electrolyte imbalance

Cancer patients selected for cisplatin-based chemotherapy were randomly divided into two groups (42 patients in each) which received either metoclopramide or ondansetron as antiemetics. Metoclopramide was given i.v. with 5 doses of 2 mg/kg starting 30 min before the cisplatin infusion and continued with one dose every 3 h. Ondansetron was given with a first injection of 8 mg i.v. 30 min before the cisplatin infusion; the patients were given 8 mg orally 5 and 10 h after the cisplatin infusion followed by 8 mg x 3 during the next two days. In the present study ondansetron was superior to metoclopramide concerning antiemetic efficacy and gave also less side-effects as diarrhea, dizziness, extrapyramidal symptoms and electrolyte imbalance (sodium, potassium, magnesium, phosphorous) during the first 24 h following the cisplatin infusion.

Comparison of ondansentron versus ondansentron plus methylprednisolone as antiemetic prophylaxis during cisplatin-containing chemotherapy

We compared the antiemetic efficacy of ondansentron versus ondansentron and corticosteroids in cisplatin-induced emesis. None of our patients had received prior chemotherapy. All patients received chemotherapy including cisplatin 100 mg/m2. Forty patients received ondansentron alone (Group A) and 40 the combination of ondansentron and methylprednisolone (Group B). Ondansentron was given at a dose of 8 mg in 100 mL N/S over 10 min by intravenous infusion. The initial dose was administered before the cisplatin and was followed by 8 mg orally in the afternoon and before sleeping the first day of chemotherapy. During the next 2 days, the patients received 8 mg orally 3 times daily. Methylprednisolone was given as an intravenous bolus of 40 mg before chemotherapy and then together with each dose of ondansentron at a dose of 16 mg orally. Group A had significantly longer duration of nausea after chemotherapy than group B (117 +/- 111 min, 62 +/- 71 min, P < 0.013). The response on emesis was also improved in group B, especially the day of chemotherapy [treatment failure: group A: 13 patients (30%) versus group B: 5 patients (11.6%), P < 0.03] and the next day [complete response: group A: 17 patients (39.5%) versus group B: 30 patients (69.7%), P < 0.005]. Patients in group B presented more sedative effects (P < 0.001) and better appetite (P < 0.02) than patients in group A. There were no other significant differences in side effects (activity, headache, constipation, etc). We conclude that corticosteroids improve the antiemetic efficacy of ondansentron in cisplatin-induced chemotherapy, and should be included in antiemetic regimens.

Rare and aggressive metastatic, axial multifocal local epithelioid sarcoma associated with paraneoplastic granulocytosis and hypoglycaemia

Epithelioid sarcoma is a rare soft-tissue sarcoma (STS; <1% of total STS) that aff ects young, usually male, adults or adolescents. In most cases, the sarcoma grows slowly (over a period of years), involves the dermis, subcutis, or deeper soft tissues in the distal extremities in 55–60% of cases. Epithelioid sarcoma is characterised by diagnostic diffi culties, both clinically and histopathologically, which results in a high frequency of initial misdiagnosis and loss of crucial treatment time. Surgical excision (amputation or wide en-bloc excision), then high-dose radiotherapy represents optimum treatment, however, this regimen is associated with a recurrence rate of 77% and a median overall survival of about 88 months for patients without distant metastases, and just 8 months for those with distant metastases. Unlike in most sarcomas, metastases aff ecting the lymph nodes are common in epithelioid sarcoma. However, the lungs are the most common site of distant metastases in epithelioid sarcoma. Furthermore, multifocal local disease, initial proximal limb or axial tumour location, regional metastases, high mitotic fi gures, necrosis, and haemorrhage or vascular invasion have a more aggressive course, and predict for a poor survival that is free from distant metastasis. Immunohistochemically, most epithelioid sarcoma express vimentin, keratin, epithelial membrane antigen (EMA), CD34 (60%), cyclin D1 and tissue polypeptide antigen (TPA). Coexpression of vimentin and keratin is thought to be characteristic of epithelioid sarcoma. A 37-year-old man was admitted to our hospital diagnosed with epithelioid sarcoma. On admission, the patient had four cutaneous lesions measuring 3–6 cm and a painful right knee. The lesions were localised at the epigastrium, right lateral abdominal area, anterior iliac crest level, spinal region at the level of L3–L5, and right buttock. According to the patient’s recent medical history, the fi rst lesion of around 1 cm seemed to develop on a surgical scar 3 months after a gastric ulcer operation. The lesion was misdiagnosed as infl ammation and was treated with antibiotics. 1 month later, a second lesion developed on his right buttock, and a biopsy by surgical excision yielded a diagnosis of epithelioid sarcoma. Microscopic examination shows nodular growth with central necrosis and haemorrhage (fi gure 1A). Immunohistochemistry showed expression of vimentin (fi gure 1B) and actin. EMA, keratin, CEA, S100p, CD30, CD31, and CD34 were negative. CT scans of the thorax and abdomen, and a bone scan found splenomegaly, multiple lung nodules, enlarged mediastinal, mesenteric, and paraortic lymph nodes, and bone metastases at L3, L5 vertebrae and at the right upper tibia (fi gure 2). Blood analyses showed leucocytosis (white blood cell [WBC] count: 23·9 × 10 cells/L; with neutrophils: 87·9%). Multiple cultures of blood, urine, sputum, and dermal lesions found no evidence of infection during the patient’s clinical course. Based on prominent leucocytosis, we measured serum granulocyte colony-stimulating factor (G-CSF). The highly increased serum G-CSF of more than 2 μg/L (normal <40 ng/L) suggested that a G-CSF-producing epithelioid sarcoma was the cause of leucocytosis. The Lancet Oncol 2006; 7: 82–84

Diffuse calcification of metastases after intensive multiagent chemotherapy in widespread osteosarcoma leading to death in a 18-year-old male: report of a case and literature review.

Multifocal osteosarcoma represents a rare and aggressive type of osteosarcoma in which multiple bone lesions are detected simultaneously in the absence of pulmonary or any other visceral organ involvement. Despite a multidisciplinary approach, overall survival remains poor and disease progresses, leading to death within 1 yr of diagnosis. Here we report a case of an 18-yr-old patient with extensively metastatic osteosarcoma developing diffuse calcification in lung, pleural, diaphragm, pericardial, subcutaneous metastases, and mediastinal lymph nodes after intensive multiagent chemotherapy. We provide an extensive review of the literature together with presentation of different aspects regarding the debate on the multicentric versus metastatic hypotheses for multifocal osteosarcoma. An update on the current understanding of the molecular features of this disease is also included.