Abstract: PURPOSE: Epidermal growth factor receptor-overexpression reported in colorectal cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted a phase II study in 57 patients with EGFR-positive advanced colorectal cancer (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as maintenance. Main biological objective was to assess sEGFR as surrogate marker of tyrosine kinase inhibition and as predictor of response. METHODS: sEGFR, evaluated by quantitative ELISA, was investigated as predictive factor both taking into account the basal value only, and its whole pattern over time. sEGFR was collected at baseline and at every 2-months assessment in 42 cases. Thirty-three patients reported CR/PR as best objective response (BOR), while nine showed SD/PD. RESULTS: Retrospectively, on average, the sEGFR values reported by both responders (CR/PR) and not responders (SD/PD) were already different at baseline (49.4 +/- 6.2 and 42.4 +/- 8.4 ng/ml respectively). This difference was statistically significant (p = 0.042). Although sEGFR trend over time confirmed the basal difference (p = 0.032), this result should be taken with caution, due to the small number of patients reporting EGFR values besides the basal one. CONCLUSIONS: Higher sEGFR at baseline was associated to BOR and may be considered a significant predictor of outcome in patients with ACC.
Abstract: BACKGROUND/AIMS: ECF is an active regimen in advanced gastric adenocarcinoma (GAC). We used ECF as an adjuvant therapy in a cohort of patients with GAC who underwent curative surgery and describe their results in terms of feasibility and outcome. METHODOLOGY: Forty-seven patients with locally advanced GAC underwent curative surgery followed by 4 to 6 courses of adjuvant ECF. Their median age was 59 years (range 32-74) and UICC stage was III-IV in 28 patients (59%). Partial or total gastrectomy was performed in 49% and 47% of cases, respectively. RESULTS: Chemotherapy was well tolerated, the main grade 3/4 toxicities being neutropenia (47%) without severe infections, and anorexia (11%). Port adverse events were recorded in 17%. There where no treatment-related deaths. With a median follow-up of 65 months, the median overall- and relapse-free survivals were 50.1 months and 42.6 months, respectively. CONCLUSIONS: The adjuvant ECF regimen is safe and feasible in resected patients with locally advanced GAC. The survival in our series compares favorably with cohorts described by others, supporting our confidence on using adjuvant ECF for patients who decide to undertake such type of treatment. ECF might be a reasonable treatment arm to be used in randomized trials of adjuvant chemotherapy.
Abstract: BACKGROUND/AIMS: This study analyzed the results of treatment of rectal cancer (tumor within 12 cm of the anal verge) with different techniques. METHODOLOGY: Two hundred and sixty-four patients who had undergone elective curative surgical resection of rectal cancer within 12cm of the anal verge were evaluated. The operative data and follow-up data were collected prospectively. Comparisons were made between patients who had different surgical procedures. RESULTS: The overall peroperative mortality rate was nil, and the morbidity 39.4%. Local recurrence occurred in 21 of the patients with a median follow-up of 34 months (range: 5-105 months). The 3-year actuarial local recurrence rates for double-stapled anastomosis, low straight anastomosis and APR were 25%, 6%, and 5%, respectively. The local recurrence rate was significantly higher for double-stapled low anterior resection than for the other types of operation (p = 0.013). On multivariate analysis reconstruction with Knight-Griffen anastomosis (p = 0.013) and tumor distance from the anal verge <6 cm (p = 0.001), were associated with local recurrence but only stage was a significant prognosticator of overall survival (p = 0.012). CONCLUSIONS: Following total mesorectal excision, the local recurrence rate was higher in patients treated with double-stapled low anterior resection than in those with termino-terminal low anterior resection or APR; survival rates were similar in these groups.
Abstract: BACKGROUND AND AIMS: Type 1 gastric neuroendocrine tumour surveillance and treatment are a matter of debate. Endoscopic, or surgical, resection and chronic somatostatin analog therapy have been proposed. Based on the favourable behaviour of this neoplasm, we performed an endoscopic and clinical follow-up in 11 patients affected by type 1 gastric neuroendocrine tumours, avoiding any specific treatment. METHODS: Between 1994 and 2006, we prospectively recorded the data of 11 untreated patients with type 1 gastric neuroendocrine tumours who underwent an endoscopic and clinical follow-up. All the patients were also evaluated by means of an abdominal computed tomography scan, somatostatin receptor scintigraphy and blood tests. RESULTS: During the follow-up (median 54 months, range 9-136), the endoscopic picture of 4 (36%) out of 11 patients changed in terms of increased number of lesions. In none of the cases were detected any lesions that exceeded 10mm in diameter, and none of the patients demonstrated any evidence of local or distant metastases. CONCLUSIONS: Our data confirm the literature data of the indolent behaviour of type 1 gastric neuroendocrine tumours and suggest that a careful endoscopic follow-up, without any treatment, might represent a reasonable and safe option in selected patients.
Abstract: In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-alpha and somatostatin analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon-alpha and somatostatin analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.
Abstract: BACKGROUND: This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994-2003. METHODS: A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years +/- 11 years, range: 24-88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 +/- 24 months; range: 3-108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed. RESULTS: Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001). CONCLUSION: A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.
Abstract: BACKGROUND/AIMS: To compare the short- and long-term outcome of older and younger patients with advanced colorectal cancer who underwent elective surgery. METHODOLOGY: Six hundred and ninety-two patients were analyzed. Four hundred and seventy-nine patients were < 70 years (group 1), and 213 were > or = 70 years (group 2). RESULTS: The overall peroperative mortality rate in younger patients was 0.8% (n = 7), and 1.4% (n = 3) in the elderly (p = NS); morbidity was 35% and 42%, respectively (p = NS). On univariate analysis, elderly patients had a worse overall survival (OS) compared to younger, when only patients undergoing postoperative chemo-radiotherapy were considered (54% OS vs. 67% OS at 5 years; p = 0.03). Using logistic regression analysis, tumor stage (p < 0.0001) and radicality of surgery (p < 0.0001), were strongly associated with OS rates in the elderly. CONCLUSIONS: Colorectal surgery for malignancy can be performed safely in the elderly. Clinical trials are necessary to understand the real advantage of adjuvant or palliative treatments in these patients.
Abstract: BACKGROUND/AIMS: The major complication for liver resection is hemorrhage. Energy sources other than electrosurgery have become popular with the promise of quick and effective vascular control. This study evaluates alternative energy sources in sealing ductal structures for use in liver resection with minimal blood loss. METHODOLOGY: Between June 1994 and December 2003, a consecutive 116 patients (59 male; 57 female; mean age: 60 +/- 11 years; range: 27-79 years) underwent surgery for primary (n = 30), metastatic liver cancer (n = 79), or benign lesions (n = 7). The extent of hepatic parenchymal division is marked on the surface with a diathermy-scored line. The arteries, veins, and bile ducts crossing the line of division are grasped, singly or in groups, by the Ligasure (Autosuture, United States Surgical Corp., Norwalk, CT) electrocautery device. RESULTS: Fifty-eight formal hepatic resections, and 58 non-anatomical wedge resection were performed. The blood loss ranged from 100 mL to 3000 mL (median: 430 mL). Only 32 patients received preoperative blood transfusions. Perioperative mortality was nil (within 30 days following surgery), and postoperative major complications were seen in 14 patients (12%). CONCLUSIONS: The Ligasure device uses bipolar electrothermal energy to coagulate the opposing walls of the target vessels. A feedback-control mechanism ensures that tissues are not charred by overcoagulation. This results in a high-burst strength vessel seal. Sealing is effective in vessels up to 7mm in diameter. Larger vessels require formal suture or stapling. This described technique is simple, rapid, safe for parenchymal division during hepatectomy, resulting in minimal blood loss.
Abstract: PURPOSE: This randomized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate (ORR) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil (ECF) as first-line advanced gastric cancer therapy. PATIENTS AND METHODS: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric carcinoma, a performance status <or= 1, and adequate hematologic, hepatic, and renal function randomly received <or= eight 3-weekly cycles of ECF (epirubicin 50 mg/m(2) on day 1, cisplatin 60 mg/m(2) on day 1, and fluorouracil [FU] 200 mg/m(2)/d on days 1 to 21), TC (docetaxel initially 85 mg/m(2) on day 1 [later reduced to 75 mg/m(2) as a result of toxicity] and cisplatin 75 mg/m(2) on day 1), or TCF (TC plus FU 300 mg/m(2)/d on days 1 to 14). Study objectives included response (primary), survival, toxicity, and quality of life (QOL). RESULTS: ORR was 25.0% (95% CI, 13% to 41%) for ECF, 18.5% (95% CI, 9% to 34%) for TC, and 36.6% (95% CI, 23% to 53%) for TCF (n = 119). Median overall survival times were 8.3, 11.0, and 10.4 months for ECF, TC, and TCF, respectively. Toxicity was acceptable, with one toxic death (TC arm). Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel (TC, 49%; TCF, 57%; ECF, 34%). Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens. CONCLUSION: Time to response and ORR favor TCF over TC for further evaluation, particularly in the neoadjuvant setting. A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed.
Abstract: BACKGROUND: A promising regimen including 5-Fluorouracil, methotrexate and oxaliplatin is reported. PATIENTS AND METHODS: Patients with untreated measurable metastatic disease received bolus 5-Fluorouracil (600 mg/m2) on days 2 and 16, modulated by methotrexate (200 mg/m2) 24 h earlier, alternated with 4 weeks of continuous infusion of 5-Fluorouracil (200 mg/m2/daily) plus oxaliplatin (130 mg/m2) on days 29 and 56, followed by 2 weeks of rest. Serum vascular endothelial growth factor (VEGF) was analyzed at baseline and before every cycle. RESULTS: Fifty-eight patients were enrolled. Objective remissions were reported in 45.6% (95% CI=34.3%, 57.3%). The median progression-free survival was 7.8 months and the median overall survival was 19.4 months. No grade 4 toxicity was reported, except for one case of diarrhea. The serum VEGF evaluated in 23 patients showed a decreasing trend during therapy. CONCLUSION: The regimen was active, well tolerated and may be a possible option in patients not suitable for radical surgery.
Abstract: BACKGROUND AND AIMS: This study reviewed the results of surgery for distal rectal cancer (where the tumour was within 6 cm of the anal verge) following the introduction of total mesorectal excision for rectal cancer in one institution. PATIENTS AND METHODS: One hundred and fifty-three patients who had undergone elective curative surgical resection of rectal cancer within 6 cm of the anal verge were included. The demographic, operative and follow-up data were collected retrospectively. Comparisons were made between patients who had different surgical procedures. RESULTS: The overall operative mortality rate was nil, and the morbidity 41%. With a mean follow-up of 37 months (range 5-100 months), local recurrence occurred in 18 of the patients. The 5-year actuarial local recurrence rates for double-stapled anastomosis, low-strength anastomosis and abdominoperineal resection (APR) were 39, 17 and 11% respectively. The local recurrence rate was significantly higher for double-stapled low anterior resection than for the other types of operation (P=0.007). On multivariate analysis type of surgery (P=0.025) and tumour stage (P=0.043), were associated with local recurrence, but only stage was a significant prognosticator of overall survival (P=0.0006). CONCLUSION: With the practice of total mesorectal excision, APR was still necessary in 40% of patients with rectal cancer within 6 cm of the anal verge. The local recurrence rate was lower in patients treated with APR than in those with double-stapled low anterior resection; however, survival rates were similar in these two groups.
Abstract: The aim of the study was to compare the short and long-term outcomes of older and younger colorectal cancer patients with advanced disease resected with a curative intent. Six hundred and ninety-two patients were analysed. Four hundred and seventy-nine patients were younger than 70 years (Group 1), and 213 were 70 years of age or above (Group 2). The overall perioperative mortality rate in the younger group was 0.8% (n = 7), as against 1.4% (n = 3) in the elderly group (p = NS). The morbidity rates were 35% and 42%, respectively (p = NS). At univariate analysis, the elderly patients had a worse overall survival compared to the younger group, when only patients undergoing postoperative chemo-radiotherapy were considered (54% vs 67% overall survival at 5 years; p = 0.03). Using logistic regression analysis, tumour stage (p < 0.0001) and radicality of surgery (p < 0.0001) correlated significantly with overall survival rates in the elderly. Colorectal surgery for malignancy can be performed safely in the elderly with acceptable morbidity and mortality rates and long-term survival.
Abstract: BACKGROUND: A phase I-II multicenter trial was conducted to define the maximum tolerated dose (MTD) according to tolerance and toxicity (primary objective), as well as to describe the clinical activity, in terms of response and survival (secondary objectives), of a combination of 5-fluorouracil (5-FU) in protracted continuous intravenous infusion (p.i.v.) with docetaxel and cisplatin for patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, World Health Organization performance status < or =1, normal hematological and renal functions, adequate hepatic function and not pretreated for advanced disease by chemotherapy, received up to eight cycles of a combination of docetaxel on day 1, cisplatin on day 1 and 5-FU p.i.v. on days 1-14 (TCF) every 3 weeks, which was escalated up to the MTD, defined by the occurrence of dose-limiting toxicity in two patients in one dose level. RESULTS: Fifty-two patients were accrued and treated (43 in the phase I part of the trial and nine additional at the recommended dose level). A median of five cycles/patient was given. The recommended dose of TCF was docetaxel 85 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1 and 5-FU p.i.v. 300 mg/m(2)/day on days 1-14. Grade > or =3 toxicities were neutropenia 79%, alopecia 46%, fatigue 23%, mucositis 10%, diarrhea 19%, nausea/vomiting 13%, neurological 4% and palmar-plantar 2%. Ten non-fatal febrile neutropenia episodes were recorded in eight patients. There were no treatment-related deaths. Among 41 patients with measurable disease (79%), we observed one complete and 20 partial responses for an overall intent-to-treat response rate of 51% (95% confidence interval 35-67%). Five patients (20%) had stable disease for > or =12 weeks (four cycles). The median overall survival was 9.3 months. CONCLUSIONS: 5-FU p.i.v. at 300 mg/m(2)/day for 2 weeks out of three could be safely added to the docetaxel-cisplatin (TC) combination, but the dose of docetaxel had to be reduced to 75 mg/m(2) in a subsequent phase II trial. This drug regimen seems to be very active in advanced gastric cancer. Comparison with both TC and ECF in a randomized SAKK trial is ongoing.
Abstract: BACKGROUND/AIMS: Various percentages of iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy have been reported in the literature. The aim of this study was to analyze a homogeneous cohort of patients in order to evaluate the evolution and management of this complication. METHODOLOGY: We retrospectively reviewed the clinical charts of 80 patients with primary or metastatic liver tumors who received 186 hepatic arterial infusion chemotherapy courses of 5-fluorouracil, cisplatin and mitomycin-C. All of the patients complaining of upper gastrointestinal symptoms during or after hepatic arterial infusion underwent esophagogastroduodenoscopy. RESULTS: Esophagogastroduodenoscopy was performed in 14 patients, all of whom had gastroduodenal ulcers. Two of ten investigated patients were Helicobacter pylori positive. All of the patients were treated with a proton pump inhibitor and five also received major analgesics. All of the ulcers healed without complications. Six patients did not continue with hepatic arterial infusion for reasons other than ulcers. Eight patients received a subsequent hepatic intra-arterial chemotherapy course, five despite the persistence of an active ulcer. CONCLUSIONS: Iatrogenic gastroduodenal ulcers are probably due to ischemia and the direct toxicity of the anticancer agents. They are Helicobacter pylori independent and do not represent an absolute contraindication for the continuation of hepatic intra-arterial chemotherapy.
Abstract: The aim was to investigate the activity of docetaxel in advanced gastric cancer either as single agent or in combination with other drugs. A systematic review was carried out using the databases of Medline, Embase and CancerLit. Results from ASCO and ESMO meetings during 2002 were also included. Eight phase II trials focused on docetaxel as a single agent. Considering collectively the 262 evaluable patients enrolled in these studies, the mean response rate (RR) was 19% (CI 95% 14-24%). Docetaxel was well tolerated with a dose-limiting myelosuppression (grade 3-4 neutropenia in 36-95% of cases). Adding fluorouracil, an RR ranging from 22% to 86% was registered, due to differences in populations studied (young vs elderly) and modalities of drug administration (continuous vs. bolus infusion). RRs for docetaxel-cisplatin combination were 56%, 37% and 36% in three phase II trials and 35% in a phase III trial. The addition of both cisplatin and fluorouracil to docetaxel did not increase toxicity. Randomized trials comparing docetaxel-cisplatin-fluorouracil with ciplatin-fluorouoracil or epirubicin-cisplatin-fluorouracil, the most commonly used regimens, are ongoing. The future results of the above phase III studies could indicate docetaxel as a key drug to improve treatment of patients with advanced gastric cancer.
Abstract: BACKGROUND: Hepatic intra-arterial chemotherapy (HIAC) leads to a higher response rate than systemic administration in untreated patients with liver metastases from colorectal cancer (CRC). The aim of this study was to evaluate the activity and safety of giving HIAC through a percutaneous catheter in pre-treated patients. PATIENTS AND METHODS: Forty-five CRC patients with liver-only or liver-dominant metastases, resistant or refractory to previous systemic therapy, were treated using a temporary trans-subclavian catheter. A 3-day chemotherapy regimen of daily 5-fluorouracil (5-FU) 1000 mg/m2/day + heparin 5000 IU/day given as a 24-hour continuous infusion, and twice daily bolus injections of cisplatin (CDDP) 10 mg/m2 and mitomycin C (MMC) 2 mg/m2, was administered every six weeks. RESULTS: One hundred and seventeen courses were administered to 45 patients (a median of three per patient: range 1-5). Of the 44 patients evaluable for response, 16 (35%) had a partial response, 15 (33%) stable disease and 12 (26%) progressive disease. Eleven of the 16 responding patients had been refractory to a previous 5-FU-based systemic therapy. The most relevant grade 3-4 toxicities included neutropenia (22%) and thrombocytopenia (15%). Gastro-duodenal ulcers occurred in nine patients. Catheter displacement was recorded during 22 out of 117 (18%) courses. CONCLUSION: HIAC with 5-FU, CDDP and MMC given through a temporary percutaneous catheter is safe and active in pretreated patients with metastatic CRC. Iatrogenic gastroduodenal ulcers are a serious but manageable complication.
Abstract: Meningeal metastases occur in 2-3% of patients with breast cancer, leading to neurological morbidity and increased mortality. The criteria for treatment choice are controversial and intrathecal chemotherapy (ITC) has no documented role in the management of this disorder. We therefore evaluated the efficacy of an ITC regimen for patients presenting with carcinomatous meningitis from breast cancer. PATIENTS AND METHODS: Patients with meningeal carcinomatosis with or without concomitant parenchymal brain metastasis, were treated with repeated courses of intrathecal chemotherapy according to the following alternated weekly schedule: Day 1: Thiotepa 10 mg, methotrexate 15 mg, hydrocortisone 30 mg; Day 5: cytarabine (Ara-C) 70 mg, methotrexate 15 mg, hydrocortisone 30 mg. Folinic acid 15 mg was given orally, every six hours after methotrexate on days 2-3 and 6-7. RESULTS: Thirteen consecutive patients were treated. The median age was 45 (range 30-67) years. Eleven patients had performance status (PS) 2-3. Nine patients had other metastatic sites; synchronous parenchymal brain metastasis were present in 5 patients. Concomitant systemic chemotherapy was administered in 5 patients and external whole brain radiotherapy in 7 patients. With 12 evaluable patients we observed no responses or improvement in symptoms. Side-effects were minimal. CONCLUSION: In our series of patients, ITC failed to provide objective response or relief in clinical symptoms. Despite evidence reported in the literature indicating symptomatic improvement after ITC in a number of patients with leptomeningeal metastasis, the results of our study confirm the controversial role of ITC. New drugs and new modalities of treatment should be studied in order to efficiently control meningeal involvement of breast cancer.
Abstract: A PCR-denaturant gradient gel electrophoresis (DGGE) method was developed for the detection of p53 and K-ras mutations in primary operable tumors and paired BAL samples of non-small cell lung cancer. Among 36 patients, 9 showed p53 exon V mutations in biopsies and in three paired bronchoalveolar lavage (BAL) specimens with a 33% concordance. Five patients presented p53 exon VI mutations in biopsies and in two paired BALs with a 40% concordance. No mutations were found in p53 exon VII either in biopsies or in paired BAL samples with 100% concordance. Exon VIII mutations were found in six primary tumors and in two BALs with a 33% concordance. Of 36 patients, we detected 7 (19.4%) with K-ras exon I mutations on tumor samples. DGGE analysis of DNA from BAL samples revealed three mutations distributed on K-ras exon I with a 42% overall concordance with respect to tumor tissue. Molecular screening by DGGE of p53-amplified DNA from BAL had cumulative 46.6% sensitivity, 100% specificity, and 77.7% accuracy. DGGE K-ras detection showed 43% sensitivity, 100% specificity, and 88.8% test accuracy. The method proposed demonstrated to be specific, accurate, and at relatively low cost but limited by low sensitivity in detecting the presence of neoplastic cells in patients with resectable non-small cell lung cancer.
Abstract: PURPOSE: A multi-centric trial was performed to explore the clinical activity, in terms of response and toxicity (primary objectives), duration of response and survival (secondary objectives), of docetaxel with cisplatin in advanced gastric cancer (AGC). PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, performance status < or = 1, normal hematological, hepatic and renal functions and not pretreated for advanced disease by chemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2 dl, cisplatin 75 mg/m2 dl) q3w. Dose escalation to 100 mg/m2 was performed in five patients and was discontinued for excessive toxicity. RESULTS: Forty-eight patients were accrued. A median of 5 cycles/patient was given. We observed 2 complete and 25 partial responses for an overall intent to treat response rate of 56% (95% CI: 41%-71%). Twelve patients had stable disease for > or = 9 weeks (3 cycles). The median time to progression and overall survival were 6.6 and 9 months, respectively. Grade > or = 3 toxicities were neutropenia 81%, anemia 32%, thrombocytopenia 4%, alopecia 36%, fatigue 9%, mucositis 9%, diarrhea 6%, nausea/vomiting 4%, neurologic 2%, and one anaphylaxis precluding treatment administration. We recorded nine episodes of non-fatal febrile neutropenia in eight patients, two of them with docetaxel at 100 mg/m2. There were no direct treatment-related deaths. CONCLUSIONS: TC is active in AGC with a high response rate in a multicentric trial. Despite its hematotoxicity, this regimen is well tolerated and can be recycled as originally planned in 78% of the cases. These results may serve as basis for further developments of docetaxel containing regimens in this disease.
Abstract: Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours. The present study evaluated immunohistochemically the prevalence of CD99 expression in a series of 68 neuroendocrine tumours of different gastrointestinal and pulmonary sites. We now report on membrane and/or granular cytoplasmic immunoreactivity in 25% of these tumours, independent of their anatomical sites. In lung neuroendocrine tumours, CD99 was preferentially confined to typical carcinoids (P=0.009). A statistically significant relationship was observed between the number of CD99 positive cells but not the immunostaining patterns and the presence of local invasion and/or distant metastases (P<0.001). Moreover, there was a tendency for CD99-reactive tumours to show a reduced proliferative activity expressed by a Ki67 index of 2% (P=0.119). The number of CD99 immunoreactive cells or patterns of immunoreactivity did not correlate with the presence of associated clinical syndrome or particular hormonal immunostaining. Although the molecular basis underlying CD99 expression in neuroendocrine tumours is still poorly understood, our data suggest that CD99 may be involved in cell-to-cell adhesion of neuroendocrine tumour cells and in downregulation of their proliferative activity.
Abstract: Hepatocellular carcinoma (HCC) represents one of the most common neoplasms worldwide. To date, curative treatment options include liver transplantation or resection. Unfortunately, most patients are detected with nonresectable or -transplantable HCC due to disease extension or comorbid factors, and are therefore candidates only for palliative treatments. Palliative medical treatments, including systemic chemotherapy, immunotherapy or hormonal manipulation, have a borderline activity on HCC and cannot be recommended outside clinical trials. A high response rate has been reported with local therapies such as transcatheter arterial embolisation, intra-arterial chemotherapy or percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a survival advantage for these treatment modalities, further investigations are required. Multidisciplinary treatment, including preoperative cytoreduction or postoperative adjuvant therapy, is currently under investigation, with encouraging survival results. HCC patients should be evaluated within clinical trials, possibly randomised and with homogeneous prognostic factors, in order that we may find the answer to all these important questions.
Abstract: BACKGROUND: Adriamycin (ADM) and ifosfamide (IFO) are the two most active agents in the treatment of soft tissue sarcomas (STS) with a clear dose-response relationship. We evaluated the feasibility and toxicity of a high-dose IFO-plus-ADM combination. PATIENTS AND METHODS: Fourteen patients with advanced disease and nine patients in adjuvant setting received IFO 12.5 g/m2 in 120-hour continuous infusion with Mesna uroprotection and ADM 20 mg/m2 on days 1-3 and G-CSF every three weeks. RESULTS: Twenty-three patients received 89 chemotherapy cycles (70 cycles at full dose). Seventeen patients received the planned treatment, and nine patients required dose reductions. We observed grade 3-4 neutropenia in 52 cycles (59%)/20 patients; grade 3-4 thrombocytopenia in 16 cycles (18%)/nine patients; grade 3-4 anaemia in 24 cycles (27%)/11 patients. Eight patients experienced febrile neutropenia and six patients required blood transfusions. CONCLUSIONS: While feasible, this regimen showed heavy toxicity. Nevertheless, 74% of the patients were able to complete the planned treatment. Adjustment of the schedule of IFO continuous infusion to improve this combination is currently under investigation.
Abstract: AIMS AND BACKGROUND: We previously reported encouraging response rates and survival with combined intra-arterial (i.a.) chemotherapy and chemoembolization in unresectable hepatocellular carcinoma. We therefore evaluated a new program combining three courses of i.a. chemotherapy with chemoembolization administered every 28 days. PATIENTS AND METHODS: The treatment regimen consisted of L-leucovorin (100 mg/m2 i.v.), fluorouracil (800 mg/m2 i.a.), and carboplatin (250 mg/m2 i.a.). Chemoembolization with mitoxantrone (10 mg/m2) plus ethiodized oil and gelatin sponge was performed immediately after. The same treatment was given every 28 days for 3 times. RESULTS: Twenty-eight patients entered the study and were assessable for response and side effects. There were 24 males and 4 females (median age, 68 yrs; range, 42-75). TNM stage was II-III in 20 and IVA in 8; 17 were Child's A and 11 Child's B. Baseline alpha-fetoprotein was elevated in 15, and there was cirrhosis in 23. Twelve patients had a partial response (43%; 95% confidence interval, 24-63%), 13 had stabilization, and 3 progressive disease. Median survival was 16.6 months (range, 2-24). Sixteen patients had grade I-II pain and 14 grade I-II fever. CONCLUSIONS: Our results indicate that the regimen is safe and well tolerated. Despite 43% objective remissions, our results do not seem better than those obtained with less intensive regimens.
Abstract: Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time (P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease.
Abstract: We describe two young women affected with syncopal episodes and occipital headache exacerbated by cough, sneezing, rising, or effort. MRI revealed in both patients type I Arnold-Chiari malformation. A craniospinal pressure dissociation with brainstem compression may be involved in the pathogenesis of headache and syncope.
