Intra-arterial chemotherapy in elderly patients with invasive bladder cancer.
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Publications and source records attributed to A Mambrini.
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In this retrospective non controlled trial we evaluated the incidence of sepsis in cancer patients in two different periods (January-June 2003 versus January-June 2004). The main difference in these two periods was that in our oncology department we changed from systemic chemotherapy to loco-regional chemotherapy using less myelosuppressive drugs and developed the domiciliary assistance. The aim of the study was to assess the incidence of sepsis in order to demonstrate a reduction of the infection related to the change of chemotherapy. In addition, this study may be able to describe the epidemiology of sepsis in cancer patients afferent to our oncology department. The incidence of sepsis was reduced in the second period from 24.3% to 6.2%. The pathogens more frequently isolated in this study were coagulase-negative staphylococci (CNS) followed by Escherichia coli and Staphylococcus aureus. Less invasive therapy may reduce infective complication of chemotherapy. The epidemiology of sepsis may be very helpful to design empiric therapeutic protocol for febrile patients that have received chemotherapy.
OBJECTIVES: This study evaluated the clinical activity and toxicity of combination chemotherapy with irinotecan and oxaliplatin in patients with advanced pancreatic cancer that had progressed despite > or =1 course of a gemcitabine-containing regimen. METHODS: Thirty patients with metastatic pancreatic cancer and Karnofsky performance status > or =70 received oxaliplatin 60 mg/m2 on days 1 + 15 and irinotecan 60 mg/m2 on days 1 + 8 + 15 every 4 weeks. Patients were assessed on the basis of clinical benefit response, changes in serum tumour marker CA 19-9, objective tumour response, time to progressive disease (TTP), and survival. RESULTS: Six patients (20%) had clinical benefit response (median duration of 7.2 months). CA 19-9 levels were reduced > or =50% from baseline in 8 patients (26%) and remained stable in 8 patients. CT scans revealed that 3 patients (10%) had a partial response and 7 (23%) had stable disease. Two patients (7%) were down-staged and underwent surgery. Median TTP was 4.1 months, median survival was 5.9 months and the 1-year survival rate was 23.3%. The most serious adverse events were grade 3-4 leukopenia in 2 patients (6%), grade 3 neuropathy in 2 (6%) and grade 3 diarrhoea in 1 (3%). CONCLUSION: Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.
Gemcitabine is considered the gold standard treatment for unresectable pancreatic adenocarcinoma. Intra-arterial drug administration had shown some interesting results in small phase II studies. In this study, patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or FLEC: 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arterially into celiac axis at a 3-week interval 3 times or 5-fluorouracil 400 mg/m2 plus folinic acid 20 mg/m2 for 5 days every 4 weeks for 6 cycles. The primary endpoint was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=0.036). Survival at 1 year increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=0.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both groups (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, the FLEC regimen given intra-arterially improved survival in patients with unresectable pancreatic adenocarcinoma.
Standard treatment for transitional cell carcinoma confined to the bladder is radical cystectomy that allow to obtain an overall 5-year disease-free survival rate only of 50-70%. It has been demonstrated that intra-arterial chemotherapy produces the same survival outcomes as radical cystectomy. This study aimed to evaluate the activity and toxicity of a bladder-sparing loco-regional treatment. Five patients with transitional cell carcinoma of the bladder (4 locally advanced and 1 pelvic relapse) were treated with doxorubycin 25 mg/m2, cisplatin 40 mg/m2 and methotrexate 50 mg/m2, all infused bolus via internal iliac arteries on day 1, every three weeks. We obtained 3 complete responses, 1 stable disease and 1 progression of disease. The treatment was well tolerated with a minimal hematological toxicity and no others major toxicity. Median disease free survival was 8 months (1-17), median overall survival was 22 months (2-55). This loco-regional regimen of chemotherapy is active and safe in locally advanced bladder cancer patients and permits a prolonged good quality of life regarding the maintenance of the physiological functions of the lower urinary tract.
Gene therapy involves the introduction of foreign DNA into somatic cells to produce a therapeutic effect. The therapeutic gene is transferred into the tumor cells using a vector. Transfer may either be in vivo in which the DNA and vector are directly introduced into the body, or ex vivo, in which cells are removed from the body, transfected with DNA and then reintroduced into the patients. The mode of gene transfer can be classified into chemical, physical and viral (1). Viruses are the most popular vectors in clinical trials because they invade cells and manipulate the cell's machinery to make viral protein; but the immune response they provoke can rapidly destroy the viral vector or the infected cells, blocking production of the useful protein. Most nonviral vector fly under the radar of immune system, but most of them have not been as efficient as viruses in shuttling genes into cells and the genes that were delivered didn't remain active for long. Intra-arterial administration can have advantages over intravenous, and intralesion routes.
Gemcitabine is considered the golden standard treatment for unresectable pancreatic adenocarcinoma. Intra-arte-rial drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared gemcitabine given weekly with a combination of 5-fluoruracil, leucovorin, epirubicin, carboplatin (FLEC) administered intra-arteriously as first-line therapy in unresectable pancreatic adenocarcinoma. Patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=.036). Survival at 1 year was increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic adenocarcinoma.
Unresectable biliary tract cancers have a very poor prognosis. No good systemic chemotherapeutic regimen is available. This study aimed to evaluated the activity and toxicity of a novel approach of combined loco-regional and systemic chemotherapy. Twenty four patients with advanced or metastatic biliary tumors were treated with epiadriamycin 50 mg/m2 and cisplatin 60 mg/m2 administered bolus in proper hepatic artery on day 1, combined with systemic continuous infusion of 5-fluorouracil 200 mg/m2/day, from day 1 to day 14, every 3 weeks. The overall response rate was 8/24 (33%), including one complete response and 7 partial responses (stable disease 46%, progression 21%). The treatment was well tolerated with a minimal hematological toxicity; the major clinical problem was the deep venous thrombosis related to central venous catheter, that occurred in 5 patients (21%). Median overall survival was 14,6 months and 1-year and 2-year survival were 54% and 38% respectively. Performance status improved in 33% of patients and weight gain more than 7% was observed in 17%. This novel combined loco-regional and systemic chemotherapeutic regimen is active and safe for advanced biliary tract cancer patients.
STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate the assessment of patients with low back pain by general practitioners (GPs) in a non-English-speaking country and to compare their behavior with AHCPR and CSAG clinical guidelines. SUMMARY OF BACKGROUND DATA: The diffusion of clinical guidelines (and their everyday application by health care professionals) is a significant problem. Because most guidelines are developed in English, concerns over their diffusion are obviously greater in non-English-speaking countries. METHODS: A questionnaire was sent to all the GPs in the province of Mantua, Italy (n = 318). The authors evaluated what examinations are routinely performed and what danger symptoms and signs prompt referral of patients. GPs indicated the frequency of their prescription of radiographs, computed tomography scans, magnetic resonance imaging, laboratory tests, and consultations. The findings were compared with a "gold standard": the AHCPR and CSAG clinical guidelines. RESULTS: The response rate was 68.2%. Only 28.0% of GPs perform all the tests considered important by the clinical guidelines, and 33.0% were aware of all the red flags. Correspondence with the clinical guideline recommendations ranged from 14.6% to 89.4%. There is a clear tendency to overprescribe examinations in acute cases, whereas in chronic cases underprescription is sometimes seen. CONCLUSIONS: In a non-English-speaking country the evaluation of low back pain by GPs does not reflect current recommendations, and the situation is seen to be worse than in English-speaking countries. Concerns over the diffusion of guidelines must therefore be considered greater in non-English-speaking countries, where thorough presentation to GPs of the existing "evidence-based" guidelines is to be recommended.
A case of solitary and metachronous breast metastases from a renal cell carcinoma is described nine years after surgery. The review of the literature proves that the breast is an unusual site for metastatic disease.
BACKGROUND: Vinorelbine (VI) and paclitaxel (TA) are among the most active single agents in the treatment of patients with breast carcinoma, and both have microtubules as their cytotoxic target. This Phase I-II study combined these 2 agents and used a 96-hour intravenous (i.v.) infusion of paclitaxel to maximize their cytotoxic activities. METHODS: Patients with metastatic breast carcinoma who were previously treated with chemotherapy were administered increasing doses of a 96-hour paclitaxel i.v. infusion from Days 1 to 5, with a first fixed dose of vinorelbine (12.5 mg/m(2) on Days 1 and 5) every 3 weeks. The dose of paclitaxel was then decreased starting from the previously established tolerated dose, and a second fixed dose of vinorelbine (15 mg/m(2) on Days 1 and 5) was given. This identified 2 acceptable doses of paclitaxel (110 mg/m(2) with VI 12.5 mg/m(2) and 90 mg/m(2) with VI 15 mg/m(2)). The latter was used in the subsequent Phase II study. RESULTS: For the 50 patients treated with any dose, the complete response (CR) and the CR plus partial response (PR) rates were, respectively, 14% and 48% (95% confidence interval [CI], 34-67%). When only the 27 patients treated with the Phase II dose were considered, the figures were, respectively, 11% and 52% (95% CI, 42-62%). The median time to progression was 26 weeks, and the median survival 51 weeks. The dose-limiting toxicity was febrile neutropenia. CONCLUSIONS: At the dose schedule identified for the Phase II study, the VI-TA-96 combination has considerable antitumor activity; pharmacoeconomic interest (it requires about half the doses of the agents administered singly); no major toxicity, except G4 neutropenia; and no need for premedication. This combination may be recommended as one of the most effective therapeutic options for patients with metastatic breast carcinoma who were pretreated mainly with anthracycline-containing chemotherapy.
A case of a 64-year-old man with eccrine carcinoma arising from hand skin is reported. At the time of diagnosis he showed bilateral pneumonic metastases. Although the patient underwent two systemic chemotherapy lines, he showed further progressive disease of the lung. For this reason a third chemotherapy line was started through thoracic stop-flow infusion. In this way, a five month stable disease had been achieved. The patient died 7 months later for progressive disease. The rarity of this disease, the uncertain treatment, the feasibility and efficacy of thoracic stop-flow infusion are underlined and further studies are suggested.
Conventionally, tumor size, axillary lymph nodes status, histologic type and grading, proliferative activity, steroid receptors have been used to predict the natural history of breast cancer. In node-negative patients with breast cancer it is most important to identify biological markers that can predict the risk of systemic relapse. These features have been used to allow selection of the best treatment. In this paper we describe the prognostic significance of new tumoral markers in breast cancer patients without axillary involvement. We analyze the prognostic role and the correlation with response to treatment of these parameters: ploidy, oncogenes, p53, epidermal growth factor receptor and cathepsin D.
Intra-arterial hepatic chemotherapy (LAHC) results in significantly higher response rate than the best systemic treatment of liver metastases from colorectal cancer, but no survival advantage has to date shown because of extra-hepatic progression. From June 1991 to December 1994, twenty patients with hepatic metastases from colorectal cancer were enrolled. All patients underwent laparotomy for the placement of an intra-arterial catheter into the gastroduodenal artery connected with a subcutaneous port. All patients underwent cholecystectomy and biopsy of liver lesion to confirm metastatic disease. Locoregional schedule was: 5-fluorouracil (5FU) 500 mg/sqm, epirubicin (EPI) 13 mg/sqm, mitomycin-C (MMC) 7 mg/sqm, in bolus every 3 weeks. Systemic therapy consisted of leucovorin 500 mg/sqm, over 2 hours and 5FU 600 mg/sqm in bolus every week. Treatment was planned over a six month period. The complete response (CR) plus partial response (PR) rate was 50% of the entire group. The median survival was 18 months and 1- and 2- and 3-year survival rates were 71%, 38% and 20% respectively. Prior to chemotherapy, LDH value and % of liver involvement were the only significant prognostic parameters. Toxicity was absent or mild and no patient stopped treatment because of side effects. Combined systemic and IAHC is an effective treatment for liver metastases from colorectal cancer, with a mild or moderate toxicity. However, more trials are needed, to improve the control of the extrahepatic disease.
Hibernomas are benign tumors derived from brown fat that most often present as painless, slowly enlarging masses in the interscapular region, the neck, the inguinal region and the mediastinum. We report one case of hibernoma of the axillary region and we review the clinical presentation, diagnostic and therapeutic of this kind of soft tissue neoplasm.
AIMS: To find a means of achieving operability very quickly without the additional discomfort of prolonging systemic chemotherapy. To improve the patient's quality of life by obtaining quick tumor reduction and decreasing systemic toxicity. MATERIALS AND METHODS: From January 1991 to January 1995, 13 patients with locally advanced breast cancer (LABC) and 8 patients with recurrent breast cancer (RBC), were treated by transfemoral Seldinger technique, with the catheter tip placed into the subclavian artery at the basis of the internal mammary artery. The patients received 5-fluorouracil (5FU) 1000 mg, epirubicin (EPI) 30 mg/m2, mitomycin (MMC) 7 mg/m2 over an infusion for 30 minutes. The cycle was repeated every two weeks for three times. RESULTS: The overall response rate was 62%. Stage IIIb and RBC patients had a response rate of 100% and 25% respectively. In respondent patients a measurable response was seen after the first cycle. Ten patients were radically operated. After a media follow-up of 21 months, the overall survival is 52% at 48 months (68% at 48 months and 65% at 34 months for stage IIIb and RBC patients respectively). CONCLUSIONS: PIAC is feasible and effective. In LABC patients it reaches 100% of response rate. Systemic toxicity was absent and the local one was mild. The interval between the starting of PIAC and operation is short. There was an optimal compliance of the patients.
The authors describe five consecutive patients with testicular non Hodgkin lymphoma, evaluate the clinical and histological characteristics and underline the importance of a chemotherapy approach both at diagnosis and at relapse. A review of the literature is carried on and particularly about the prognostic factors, the correlation with Ebstein Barr virus and the more recent integrated therapeutical approaches.