Onycholysis secondary to multiple paclitaxel 1-hour infusions: possible role for its vehicle (Cremophor EL).
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Antineoplastic Agents, Phytogenic↗
Biomedical subjects
U De Giorgi
Publications and source records attributed to U De Giorgi.
Tyrosine kinase inhibitor imatinib mesylate as anticancer agent for advanced ocular melanoma expressing immunoistochemical C-KIT (CD 117): preliminary results of a compassionate use clinical trial.
Imatinib mesylate (IM), is a selective and competitive inhibitor of tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 200-600 mg, the majority of patients with chronic myeloid leukaemia, Philadelphia chromosome-positive acute lymphoblastic leukemia expressing the BCR-ABL fusion protein and gastrointestinal stromal tumours (GIST) achieve a bio-molecular and clinical response, frequently complete, associated with limited toxicity. Several other human cancers, as small-cell lung carcinoma, melanoma, seminoma, some sarcomas, and adenoid cystic carcinomas may over-express KIT or PDGF-R, and clinical trials to evaluate the role of IM in the treatment of such cancers are currently ongoing. We determined c-KIT with Dako CD 117 antibody in 5 cases of advanced ocular melanoma (OM) and we found positive immuno-reactivity for CD 117 in three patients. We treated all patients with palliative-use IM at the oral dose of 400 mgr daily. We obtained in expressing positive immuno-reactivity for CD 117 patients: a reduction of malignant ascites in one, a partial remission in the neck nodes in another, and progression of liver metastases in the third. Evidences of progression has been reported in the other two patients expressing negative immuno-reactivity for CD 117. We conclude that the effect of IM should be assessed only in OM with positive immuno-histochemical c-kit (CD 117) expression. IM might be a potential therapeutic strategy for these patients.
Adult↗
Primary ovarian carcinoid presenting as acute abdomen.
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Abdomen, Acute↗
Intraoperative radiotherapy: current thinking.
Intraoperative radiotherapy (IORT) refers to the delivery of irradiation at surgery. A large single dose of irradiation is delivered to a surgically defined area, while uninvolved and dose-limiting tissues are displaced, the final goal of IORT being enhanced locoregional tumour control. IORT is used in most modern protocol studies as a boost radiation component of multidisciplinary treatment approaches. More recently, high activity radiation sources or mobile operating room treatment machines are used to facilitate the IORT procedure. Clinical experiences have shown that IORT may improve local control and disease-free survival, especially when used in adjuvant setting, combined with external beam irradiation in some neoplasms such as cancer of the stomach, pancreas, colorectum, and soft tissue sarcoma.
Colorectal Neoplasms↗
Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.
PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.
Adult↗
Intra-arterial hepatic chemotherapy (IAHC) for liver metastases from colorectal cancer: need of guidelines for catheter positioning, port management, and anti-coagulant therapy.
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Antimetabolites, Antineoplastic↗
Hyperthermia and hypoxia: new developments in anticancer chemotherapy.
It has been demonstrated in vitro and in vivo that hyperthermia can enhance the cytotoxicity of some chemotherapeutic agents. The in vivo studies have demonstrated that the thermal advantage is maximized at mild temperatures such as at 40.5--43 degrees C. Thermo-chemotherapy is widely applied in limb perfusion and intraperitoneal chemotherapy. Hypoxia in solid tumours leads to resistance to most anticancer drugs and appears to accelerate malignant progression and increase metastasis. The recent development of new drugs highly toxic to hypoxic cells may bring new strategies in anticancer treatments and move this condition from being a problem to a new tool in cancer control.
Antineoplastic Agents↗
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
AIM: Our experience of pre-operative intraarterial (i.a.) vs intravenous (i.v.) infusion of cisplatinum (CDP) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported. METHODS: Two successive randomized studies were performed. In the first, pre-operatively, CDP i.a. vs CDP i.v. was applied in combination with high-dose methotrexate (HDMTX) and adriamycin (ADM) within a three-drug regimen. In the second, a combination of HDMTX, ADM and IFO, within a four-drug regimen was tested. RESULTS: The rate of responses to chemotherapy (tumour necrosis > or = 90%) was significantly higher (P<0.04) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen (76%vs 62%). According to the route of CDP infusion, in the three-drug regimen the rate of responses was significantly higher (P=0.004) in patients treated with i.a. CDP (77%) than in patients treated i.v. (46%); with the four-drug regimen the rate of response was not significantly different in patients treated i.a. (81%) and in patients treated i.v. (71%). No significant differences in the rates of limb salvages, local recurrence and event-free survival (EFS) were seen between the i.a. and the i.v. groups. CONCLUSION: In the treatment of osteosarcoma of the extremity, the i.a. infusion of CDP does not offer any significant advantage when this drug is used within an aggressive, multiagent, pre-operative four-drug regimen.
Adolescent↗
Glaucoma and paclitaxel.
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Antineoplastic Agents, Phytogenic↗
Global approach to hepatic metastases from colorectal cancer: indication and outcome of intra-arterial chemotherapy and other hepatic-directed treatments.
Liver metastases of colorectal cancer is present in more than 20% of new diagnosed patients and in 40-60% of relapsed patients. It is a life-threatening prognostic aspect. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). Angiography and intraoperative ultrasonography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems usefull combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, percutaneous radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review will report the possibilities of intra-arterial chemotherapy and other novel hepatic-directed approaches to the treatment of liver metastases from colorectal cancer.
Antineoplastic Agents↗
Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases.
The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1-5 and cisplatin 20 mg/m2 days 1-5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1-5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. In our hands, VeIP seems to be less satisfactory as mobilizing treatment than VIP, possibly due to a superior number of premobilization courses of chemo therapy in some patients. Moreover, high-dose cyclophosphamide remains a good alternative for mobilizing patients refractory to salvage chemotherapy.
Adolescent↗
Treatment of small cell lung cancer.
Small cell lung cancer represents approximately 25% of all lung cancers. During the 1980s enormous efforts have been made to try to create a breakthrough in this peculiar disease but, despite the excellent results obtained in the early 1980s with multidrug chemotherapy, no significant improvements have been achieved in the 1990s. Overall response rates are in the range of 60-90% for patients with limited disease and 40-70% for those with extended disease, with pathological remissions in the range of 20-50%. Nevertheless, the majority of patients with small cell lung cancer continues to relapse and ultimately dies of the disease. New strategies under clinical evaluation are the multimodality approach, such as concurrent chemoradiation, and the use of dose-intensive regimes or even high-dose chemotherapy supported by autologous haemopoietic rescue. In the near future other strategies will be possible, owing to the tremendous increase in the knowledge of biological properties of this disease. This article aims to summarize the research so far, the current strategies and the probable future of the treatment of small cell lung cancer.
Carcinoma, Small Cell↗
[Adjuvant concomitant chemotherapy in pancreatic cancer].
Pancreatic cancer is a leading cause of cancer death. Despite improvement in diagnosis and treatment in the last 15 years, mortality rates essentially equal the incidence of the disease. Combination treatment with chemoradiation yields up to now better results than chemotherapy or radiotherapy given alone in consideration of substantial radio and chemoresistance of the cancer cells. This study will review the most important literature data about combination adjuvant treatment and preoperative (primary) chemoradiation in pancreatic cancer. Some other reports will be given on locoregional chemotherapy and finally a brief view on a possible perspective for promising future treatments coming from data of molecular pathology. Adjuvant chemoradiation after surgery has been shown to be superior to operation alone in potentially resectable pancreatic cancer in many studies, in terms both of local control and median overall survival. Unfortunately, a consistent percentage of patients cannot receive adjuvant treatment since late recovery after surgery or post-operative morbidity. Owing to this last reason, many authors prefer primary chemoradiation in potentially resectable pancreatic cancer; neoadjuvant treatment find out its background in other relevant biological and clinical evaluations. Some studies report encouraging results with primary chemoradiation using 5-fluorouracil. Other experiences with relatively new drugs, with potent radiosensiting effect, such as gemcitabine or taxol are going on; many of these are phase I studies. Clinical research in the field of preoperative treatment is up to now emerging in some important Oncological Institutions. The principal actual aim seems to be that of forsee periods of treatment which will be brief and use the dose of chemotherapy that is active, giving acceptable toxicity. Ongoing trials will give, in the next years, the answer about the improvement of efficacy of treatments largely expected by all researchers.
Antineoplastic Combined Chemotherapy Protocols↗
A sequential chemo-radiotherapeutic treatment for patients with malignant gliomas: a phase II pilot study.
BACKGROUND: The purpose of our study was to evaluate the activity and toxicity of a sequential chemo-radiotherapeutic treatment on the basis of an earlier report by The Johns Hopkins Oncology Center. MATERIALS AND METHODS: Eighteen patients with histologically diagnosed malignant gliomas entered the study. Fifteen patients had glioblastoma multiforme (83%). BCNU (40 mg/sqm/die) and Cisplatin (40 mg/sqm/die) were administered concurrently for 3 days every 3-4 weeks. Radiotherapy consisted of 45 Gy whole cranial irradiation plus a 15 Gy boost on the preoperative volume. RESULTS: Thirteen patients had measurable disease and were evaluable for response. After chemotherapy we obtained 3 CRs (complete remission) and 4 PRs (partial remission) (RR (response rate 54%). Three PRs were converted to CRs after radiotherapy, for a complete remission rate of 46% (6/13). The median duration of response was 10 months. The median survival of the entire patients population was 9 months with 33% survival rates at 1 year. Hematological toxicity grade 4 in one patient and grade 3 in two patients were the major complications due to chemotherapy. CONCLUSIONS: Our sequential chemo-radiotherapeutic regimen appears to have significant activity in adults with newly diagnosed high-grade gliomas.
Adult↗
Locoregional therapy for liver metastases from colorectal cancer: the possibilities of intraarterial chemotherapy, and new hepatic-directed modalities.
Liver metastasis of colorectal cancer is a life-threatening prognostic factor. Hepatic resection, when possible, is the best therapeutic modality, although the overall survival rate is still low (30%). The diagnosis has been carried out by clinical examination, abnormal alkaline phosphatase, lactic acid dehydrogenase and tumor markers, abdominal liver echography and computed tomography scan. Angiography and intraoperative echography are useful for resection. The number of hepatic metastases and the surgical margin are probably the most significant prognostic factors. Colorectal cancer may spread predominantly to the liver making regional treatment strategies viable options. Subtotal hepatic resections and segmentectomies are potentially curable procedures for single or small numbers of hepatic metastases without other sites of disease. However, there have been no prospective randomized trials comparing patients with unresected liver metastases and resected metastases. Regional chemotherapy with floxuridine seems useful combined with hepatic resection or as palliative therapy. Gastric ulcer and biliary sclerosis are the main related toxicities. Patients with localized, unresectable hepatic metastases or concomitant bad medical condition may be candidates for radiation, percutaneous ethanol injection, cryosurgery, radiofrequency, hypoxic flow-stop perfusions with bioreductive alkylating agents, hepatic arterial ligation, embolization and chemoembolization. These new hepatic-directed modalities of treatment are being investigated and may offer new approaches to providing palliation and prolonging survival. This review reports the possibilities of intraarterial chemotherapy and other novel hepatic directed approaches to the treatment of liver metastases from this common disease.
Antineoplastic Agents↗
Amifostine (Ethyol) as modulator of hepatic and biliary toxicity from intraarterial hepatic chemoembolization: results of a phase I study.
BACKGROUND/AIMS: Hepatic and biliary toxicity are still significant problems after intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. In about 30-60% of the patients hepatic and biliary toxicity are the limiting aspects of intraarterial hepatic chemoembolization and exclude a lot of patients from a repeated beneficial treatment. Amifostine (Ethyol) is a prodrug that must be dephosphorylated to the free thiol in which form it can detoxify free oxygen radicals generated by radiation, hypoxia and by drugs such anthracyclines, platinum analogues and alkylating agents. Amifostine as inactive prodrug is primarily metabolized at the tissue site by membrane alkaline phosphatase, which is highly active in the cell membranes of normal endothelial cells and biliary tree cells but not in the cell membranes and neovascular capillaries of tumor. When dephosphorylated to WR-1065, amifostine is rapidly taken up into normal liver cells by a carrier-mediated facilitated diffusion transport process. The resulting high thiol content in normal liver tissue (biliary cells and hepatocytes) compared with the negligible concentration in liver metastases from large bowel cancers probably provides for selective drug resistance to intraarterial hepatic chemoembolization protecting normal tissue and allowing full therapeutic effect on tumor. METHODOLOGY: From May 1997 we planned a phase I study in patients receiving intraarterial hepatic chemoembolization for liver metastases from large bowel cancers. We started at 200 mg/m2 dissolved in 250 cc of normal saline given in 15 min in the intrahepatic artery 20 min before an intraarterial hepatic chemoembolization consisting of mitomycin 10 mg/m2, epirubicin-50, cisplatin-60 diluted in 10 mL of contrast media, mixed in 15 mL of lipiodol UF followed by a gelfoam powder solution until stagnation of the flow. The escalating dose, every 3 patients, was: 200 mg/m2, 250 mg/m2, 300 mg/m2, 350 mg/m2. RESULTS: Toxicity has been observed at 350 mg/m2: 1 patient reported transient hypotension (Blood pressure 70/50 mm Hg), 1 patient had skin flushing and dyspnoea. 300 mg/m2 are well tolerated and seem to reduce the level of transaminases, lactic acid dehydrogenase, and gamma-glutamyl transferase. Also the duration of necrotic damage, always observed after intraarterial hepatic chemoembolization, seems shorter compared with historical controls. CONCLUSIONS: Amifostine can be certainly administered at 300 mg/m2 as intraarterial infusion and could be a significant step to ameliorate the therapeutic ratio of intraarterial hepatic chemoembolization.
Amifostine↗