ABSTRACT
BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/secondary , Nivolumab/pharmacology , Nivolumab/therapeutic use , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Prospective Studies , Retrospective StudiesABSTRACT
BACKGROUND: Various conservative treatments and surgical techniques have been reported in the literature as efficient and feasible measures to treat the cubital tunnel syndrome. However, there has been no consensus on the best management of the syndrome, and uniform standardised guidelines have not yet been accepted or introduced. With our study, we present our experience on the clinical efficacies and outcomes of the surgical techniques of neurolysis alone and neurolysis associated with ulnar nerve anterior transposition at the elbow joint in patients with neuropathic symptoms due to cubital tunnel syndrome. MATERIALS AND METHODS: A total of 107 patients with cubital tunnel syndrome were retrospectively enrolled, surgically treated and followed up in our study. The cohort was divided into two groups: 41 patients treated only with neurolysis of the ulnar nerve (Group 1), and 66 patients treated with neurolysis and anterior transposition (Group 2). Of the participants, 35 were women and 72 were men. The average age was 54 years. Significant comorbidities were preoperatively diagnosed in 26 patients. Conservative measures had been considered, followed by surgical management if appropriate. A pre-op electromyography was performed for all patients. All surgical procedures were performed by the same surgical team. A post-operative follow-up was carried out, and the findings were recorded. The "McGowan" and "Wilson and Krout" classifications and the DASH score were used. A satisfaction questionnaire was administered to all patients post-operatively at 2 weeks). RESULTS: Ulnar nerve neurolysis and anterior transposition surgery were all successfully performed. Overall complications were post-operative haematoma (8%) and wound problems (5%). In 6% there was recurrence of symptoms. In 11% there was no improvement of symptoms. Pre-op McGowan classifications for groups 1 and 2 were 0% and 0% (grade 0), 21% and 24% (grade 1), 46% and 44% (grade 2), and 33% and 34% (grade 3), respectively. The post-op McGowan classifications were 34% and 37% (grade 0), 39% and 40% (grade 1), 23% and 20% (grade 2), and 4% and 3% (grade 3), respectively. The post-op Wilson and Krout classifications were 45% and 46% (excellent), 26% and 28% (good), 19% and 15% (fair), and 10% and 11% (poor), respectively. The DASH score means for groups 1 and 2 were 14.8 and 15.2, respectively. A negative Froment's sign was present in 73.2% and 71.2%, respectively. In Group 1, the post-op satisfaction questionnaire scores were 0 for one patient, 1 for four patients, 2 for seven patients, 3 for ten patients, 4 for twelve patients and 5 for seven patients. In Group 2, the post-op satisfaction questionnaire scores were 0 for three patients, 1 for nine patients, 2 for twelve patients, 3 for fifteen patients, 4 for eighteen patients and 5 for nine patients. CONCLUSIONS: In our experience, the surgical technique to treat the cubital tunnel syndrome most efficiently and feasibly has not yet been established in terms of indications and outcomes. This is supported by the data present in the international literature. Good and similar results were obtained with neurolysis alone and neurolysis associated with anterior transposition of the ulnar nerve (in line with the international data). In conclusion, more high-quality studies of greater statistical power are needed to provide a consensus on the surgical indications and techniques to treat the cubital tunnel syndrome and to establish internationally standardised guidelines.
Subject(s)
Cubital Tunnel Syndrome , Cubital Tunnel Syndrome/surgery , Decompression, Surgical , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Ulnar Nerve/surgeryABSTRACT
BACKGROUND: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. RESULTS: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. CONCLUSION: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.
Subject(s)
Bevacizumab/therapeutic use , Breast Neoplasms/drug therapy , Interleukin-8/genetics , Nitric Oxide Synthase Type III/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Female , Genetic Association Studies , Humans , Middle Aged , Polymorphism, Restriction Fragment Length , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Oxaliplatin (Oxa) is widely used in metastatic colorectal cancer (mCRC), but currently there are not valid predictors of response to this drug. In the control arms both of OPUS and PRIME studies Oxa seems more active in patients with mCRC with mutated (mt) KRAS than in those with wild type (wt) KRAS. Recently we have retrospectively confirmed this suggestion, therefore we have hypothesized that the mutational status of KRAS could influence the expression of ERCC1, one of the main mechanisms of Oxa resistance. MATERIAL AND METHODS: We used four cell lines of colorectal cancer: two KRAS wild type (wt) (HCT-8 and HT-29) and two KRAS mt (SW620 and SW480). We evaluated the sensitivity of these cell lines to Oxa by MTT-test as well the ERCC1 levels before and after 24 h exposure to Oxa by Real-Time PCR. We silenced KRAS in a KRAS mt cell line (SW620LV) to evaluate the impact on Oxa sensitivity and ERCC1 levels. Lastly, ERCC1 was also silenced in order to confirm the importance of this protein as an Oxa resistance factor. RESULTS: The KRAS mt cell lines resulted more sensitive to Oxa (OR 2.68; IC 95% 1.511-4.757 p<0.001). The basal levels of ERCC1 did not show significant differences between KRAS mt and wt cell lines, however, after 24 h exposure to Oxa, only the wt KRAS lines showed the ability to induce ERCC1, with a statistically significant difference (OR 42.9 IC 95% 17.260-106.972 p<0.0005). By silencing KRAS, sensitivity to Oxa was reduced in mt KRAS cell lines and this effect was associated with the acquisition of ability to induce ERCC1. Silencing of ERCC1, in turn, enhanced the sensitivity to Oxa in wt KRAS cell lines and restored sensitivity to Oxa in SW620LV cell line. CONCLUSION: KRAS mutated cell lines were more sensitive to Oxa. This feature seems secondary to the inability of these cells to induce ERCC1 after exposure to Oxa. Thus, KRAS mutational status might be a predictor of response to Oxa in CRC surrogating the cell ability to induce ERCC1.
ABSTRACT
Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes.
Subject(s)
Immunotherapy , Neoplasms/immunology , Neoplasms/therapy , HumansABSTRACT
OBJECTIVES: Although emerging data suggest that zoledronic acid (Zol) may have different anti-tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti-tumoural and anti-angiogenetic effect of zoledronic acid in non-small-cell lung cancer (NSCLC) cells. MATERIAL AND METHODS: We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti-angiogenic activity and apoptotic responses to it. RESULTS: We observed that highest Zol concentration (100µm) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P=0.0001). Zol concentration from 5 to 100µm for 2 days induced significant concentration-dependent cell death in adherent cells. Furthermore, Zol (10-100µm) induced dose-dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium. CONCLUSION: Taken together, these results support a possible anti-cancer and anti-angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti-cancer agent in non-small-cell lung cancer.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Lung Neoplasms/drug therapy , Apoptosis , Cell Line, Tumor , Cyclins/genetics , Cyclins/metabolism , G1 Phase , Humans , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Survivin , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Zoledronic AcidABSTRACT
OBJECTIVES: Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction. METHODS: After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement. RESULTS: Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy. CONCLUSIONS: This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.
Subject(s)
Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Gases , Pneumatosis Cystoides Intestinalis , Portal Vein/pathology , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cetuximab , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Pneumatosis Cystoides Intestinalis/chemically induced , Pneumatosis Cystoides Intestinalis/pathology , Pneumatosis Cystoides Intestinalis/surgery , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Tegafur/administration & dosage , Tegafur/adverse effectsABSTRACT
We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m(-2), day 1; folinic acid, 200 mg m(-2); and 5-fluorouracil: as a 400 mg m(-2) bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m(-2), from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Liver Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Male , Middle Aged , Neoadjuvant Therapy , Survival Analysis , Treatment OutcomeABSTRACT
5-Fluorouracil (5-FU) is the main drug used in the treatment of advanced gastric cancer. Combination chemotherapy is not always superior to 5-FU alone, especially when biomodulators are also administered. In an attempt to exploit all the cytotoxic mechanisms of 5-FU, we carried out a pilot study with a double route of administration of 5-FU (intravenous bolus and continuous infusion) and a multiple modulation of 5-FU by methotrexate (MTX), 6S-leucovorin (6S-LV) and cisplatin (CDDP). A group of 30 patients affected by advanced gastric cancer was treated with MTX 50 mg/m2 and 5-FU 400 mg/m2 as an i.v. bolus on day 1, followed by a 5 day i. v. continuous infusion of 5-FU 600 mg/m2/day and 6S-LV 100 mg/m2/day; on day 3 CDDP 100 mg/m2 was also administered. The regimen was repeated every 4 weeks. Six partial responses (20+/-14. 3%), 12 stable diseases (40+/-17.5%) and 12 progression (40+/-17.5%) were observed in an intent-to-treat analysis. Median survival was 7 months. All responding patients had performance status 0-1. Grade 3-4 toxicity was mainly gastrointestinal, but grade 3-4 anemia and leucopenia were also recorded. The schedule has low activity. The use of different modulators and way of administration of 5-FU does not provide advantages in advanced gastric cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Administration Schedule , Drug Synergism , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Pilot Projects , Stomach Neoplasms/pathologyABSTRACT
In order to explore the activity of a combination of vinorelbine (VNL) and alternating cisplatin (CDDP) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), a phase II study was performed. Seventy chemoradiotherapy naive patients with NSCLC, stage IIIA, IIIB and IV disease, PS (ECOG) =2, were treated with CDDP 40 mg/m(2) on days 1, 2, 3, IFX 1,800 mg/m(2) on days 22, 23, 24 and VNL 30 mg/m(2) on days 1, 8, 22, 29 every 6 weeks up to 6 courses. In the 67 evaluable patients, an objective response rate was observed in 47.8 +/- 12% (95% CI) with complete responses in 6%; responses occurred more frequently in patients with locally advanced disease (stage IIIA/IIIB) and/or performance status 0. The median duration of survival was 12 months: 19.9 months in stage III patients who received an integrated treatment and 10 months in metastatic disease. The median time to treatment failure was 10.5 months. Toxicity was mainly hematological, even though it was not dose-limiting and easily manageable. This combination seems to be active, and the good safety profile is probably the result of the use of an alternating schedule of CDDP and IFX. Median overall survival was also encouraging in stage IV disease. The prolongation of survival obtained when surgery and/or radiotherapy is applicable needs confirmation through a larger study.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/secondary , Cisplatin/administration & dosage , Drug Administration Schedule , Female , Humans , Ifosfamide/administration & dosage , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Although many drug combination therapies have been proposed, there is no standard therapy for patients with advanced gastric carcinoma. The superiority of combination therapy over monochemotherapy has not been demonstrated convincingly. To explore the role of monochemotherapy, the authors evaluated 5-fluorouracil (5-FU), modulated by 6S-leucovorin (6S-LV) and a cisplatin-containing regimen, which was comprised of epirubicin, etoposide, and cisplatin with the addition of the reversal agent lonidamine (EEP-L). METHODS: After stratification according to performance status (PS) and resection of the primary tumor, 72 patients with advanced gastric carcinoma were randomized to 2 parallel Phase II trials with 5-FU/6S-LV and EEP-L, respectively. Thirty-six patients in Study A received bolus 6S-LV, 100 mg/m2, followed by bolus 5-FU, 370 mg/m2, on Days 1-5 and 36 others in Study B received epirubicin, 30 mg/m2, on Days 1 and 5; etoposide, 100 mg/m2, on Days 1, 3, and 5; cisplatin, 30 mg/m2, on Days 2 and 4; and lonidamine, 150 mg/day. RESULTS: There were 6 partial responses (18.2%) (95% confidence interval [CI] +/- 13.2) in Study A and 7 partial responses (21.9%) (95% CI +/- 14.3) in Study B. Partial responses were more frequent in patients with resected tumors or with an Eastern Cooperative Oncology Group PS of 0-1. The median duration of response was 8.8 and 8.3 months, respectively, in Study A and Study B. The median survival reached 8 months in Study A and 9 months in Study B. In the whole population of patients survival was significantly higher in patients with a PS of 0-1 (P < 0.05). Patients with a PS of 0-1 and a resected tumor had the significantly longest survival both in EEP-L treated patients and in all evaluable patients in the two studies. The most frequent World Health Organization Grade 3-4 toxic effects were gastrointestinal in Study A and hematologic in Study B. No treatment-related death was observed. CONCLUSIONS: The efficacy of 5-FU, modulated with 6S-LV, is moderate in patients with advanced gastric carcinoma, similar to cisplatin-containing regimens. PS and other prognostic factors could influence the response rate, which does not appear to be a reliable parameter for evaluating the outcome of chemotherapy trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Cisplatin/administration & dosage , Drug Administration Schedule , Epirubicin/administration & dosage , Etoposide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Indazoles/administration & dosage , Leucovorin/administration & dosage , Male , Middle Aged , Prognosis , Quality of Life , Stomach Neoplasms/mortality , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) complicating cirrhosis has a high intrahepatic recurrence rate after treatment by surgical resection or percutaneous ethanol injection (PEI). In this study, certain clinical, biochemical, and pathologic parameters were evaluated as risk factors for intrahepatic tumor recurrence in liver segments different from that of the first neoplasm in a group of 57 cirrhotic patients with single HCC < 5 cm treated by PEI. METHODS: After PEI treatment of HCC, the patients were followed for a mean period of 33 +/- 16 months. The following pretreatment parameters were evaluated as predictors of tumor recurrence: age, gender, Child-Pugh score, hepatitis B virus surface antigen, hepatitis C virus antibodies, alanine aminotransferase, aspartate aminotransferase, alpha-fetoprotein (AFP) level before PEI, alcohol abuse, HCC size, HCC ultrasound pattern, HCC histologic grade, HCC capsule, and time from cirrhosis diagnosis. Furthermore, the posttreatment parameters of the AFP level 1 month after PEI and recurrence of HCC in the same liver segment were also evaluated. RESULTS: The cumulative 4-year intrahepatic recurrence rate of HCC was 62%. The log rank test indicated that, among pretreatment parameters, time from cirrhosis diagnosis > 6 years (P = 0.05) and AFP level before PEI of > 25 ng/mL (P = 0.00005) were significantly linked to tumor recurrence. Cox's proportional hazards model showed that only AFP level before PEI was independently associated with recurrence (P < 0.002). With regard to posttreatment parameters, an AFP level 1 month after PEI of > 13 ng/mL was shown to be significantly related to tumor recurrence by the log rank test (P < 0.0001). CONCLUSIONS: Cirrhotic patients with single HCC treated by PEI who have slightly increased serum levels of AFP before and/or after PEI treatment are at increased risk of intrahepatic tumor recurrence and should undergo a close follow-up program.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Ethanol/therapeutic use , Liver Cirrhosis/complications , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/epidemiology , Neoplasms, Second Primary/epidemiology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Humans , Italy/epidemiology , Liver Neoplasms/blood , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/blood , Neoplasms, Second Primary/pathology , Proportional Hazards Models , Risk FactorsABSTRACT
p53 overexpression was studied by immunohistochemistry in 96 consecutive colorectal cancer patients, subdividing positive specimens according to two staining patterns: cytoplasmic or nuclear. Forty-seven per cent of the cases were p53 positive, a significant correlation being found with Dukes' stage (P = 0.0036). A prevalence of nuclear staining was observed in Dukes' B and cytoplasmic in Dukes' D stages. After 36 months, 23% of the patients had a recurrence, and 45% were p53 positive, all Dukes' C-D stage with cytoplasmic staining. The Kaplan-Meier curve showed a significant correlation between p53 cytoplasmic staining and disease-free survival period (P = 0.002). With respect to disease-free survival, the Cox proportional hazard regression test, comparing p53 positivity with Dukes' stage, showed the latter to be the most significant variable. In our series of patients, advanced Dukes' stage tumours were localised in the right colon, where a higher percentage of p53 positivity (67% versus 40% of the left side), as well as a higher frequency of cytoplasmic staining was observed. In conclusion, from the data obtained, a strong correlation between p53 cytoplasmic staining and patient prognosis is clearly indicated.
Subject(s)
Biomarkers, Tumor/metabolism , Colonic Neoplasms/metabolism , Neoplasm Proteins/metabolism , Rectal Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Aged, 80 and over , Cell Nucleus/metabolism , Colonic Neoplasms/pathology , Cytoplasm/metabolism , Disease-Free Survival , Female , Follow-Up Studies , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , Rectal Neoplasms/pathologyABSTRACT
Modulation of 5-fluorouracil (5-FU) is currently being investigated in advanced colorectal cancer. In an attempt to improve the results obtainable for the association of 5-FU and leucovorin, we decided to add cisplatin to 5-FU and (6S)-leucovorin (S-LV) after disease progression. The hypothesis was that a pharmacological enhancement of the efficacy of 5-FU would result in responses in 5-FU-unresponsive patients or in a second response in previously responding patients. A group of 28 5-FU+S-LV-pretreated patients, with advanced measurable colorectal cancer, were treated with 80 mg/m2 cisplatin on day 1, 80 mg/m2 S-LV and 370 mg/m2 5-FU as an i. v. bolus for 5 consecutive days every 4 weeks. We obtained 3 partial responses (response rate: 11 +/- 11%), while 11 patients had stable disease (39 +/- 18%). Among the 3 responders, 1 patient had earlier achieved a partial response, a second stable disease and 1 had disease progression after the previous 5-FU+S-LV treatment. The median survival time for all 28 patients was 11 months. Toxicity was minimal and consisted of mild and reversible gastrointestinal symptoms and myelosuppression. We believe that further studies must be carried out to establish the real impact of the synergism between cisplatin, 5-FU and S-LV in untreated patients.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/pharmacology , Colorectal Neoplasms/drug therapy , Fluorouracil/pharmacology , Adenocarcinoma/secondary , Adult , Aged , Cisplatin/administration & dosage , Colorectal Neoplasms/pathology , Drug Resistance , Drug Synergism , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Remission Induction , Survival AnalysisABSTRACT
Primary gastrointestinal Lymphoma is a relatively infrequent tumor, who could be effectively treated with both surgery and chemotherapy or radiotherapy. The design of treatment depends on prognostic factors, namely stage and histologic grade. The most functional staging system seems that of Mushoff, while the recent concept of "Mucosa-associated lymphoid tissue" has allowed to correlate the histologic grading with prognosis. Surgery is the most used therapeutic approach in IE and IIE stages, but both chemotherapy and radiotherapy or their combination seem to have similar activity. Adjuvant chemo- and/or radio-therapy after surgery increases survival compared to surgery alone. Chemotherapy is the treatment of choice in more advanced stages.
Subject(s)
Gastrointestinal Neoplasms/therapy , Lymphoma, Non-Hodgkin/therapy , Combined Modality Therapy , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/radiotherapy , Gastrointestinal Neoplasms/surgery , Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Lymphoma, Non-Hodgkin/surgeryABSTRACT
Thirty-one patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of folinic acid, fluorouracil, vincristine, and mitomycin (F-FOMi). Eight partial responses (26%), eight stable disease (26%), and 15 progressive disease (48%) were obtained. Patients with performance status (PS) 0-1 had a significantly better response rate than those with PS 2-3. Overall actuarial survival was 10 months. Toxicity was mild and mainly gastrointestinal with mucositis and diarrhea. F-FOMi seems to be comparable to regimens more widely used in the treatment of NSCLC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Mitomycin/administration & dosage , Vincristine/administration & dosageABSTRACT
Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosphamide, adriamycin and fluorouracil (CAF); or CMF and CAF. Partial response occurred in five patients (15 +/- 12%), stable disease occurred in 15 patients (45 +/- 17%) and progressive disease occurred in 13 patients (40 +/- 17%). The median duration of response was 5 months. The median actuarial survival was 11 months. Toxicity was mild, even in patients who had previously received anthracyclines; generally it was mainly hematological. We thus recommend mitoxantrone-containing regimens as salvage chemotherapy in advanced breast cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Salvage Therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Humans , Methotrexate/administration & dosage , Middle Aged , Mitomycin/administration & dosage , Mitoxantrone/administration & dosageABSTRACT
BACKGROUND: The influence of cancer on antipyrine metabolism is under debate. METHODS: To assess the functional activity of a liver with solid metastases from primary colorectal cancer, antipyrine metabolism was studied after the drug was administered orally (18 mg/kg body weight) to 55 healthy volunteers, 62 patients with well-compensated cirrhosis, and 42 patients with small (Class A) or massive (Class B) metastatic liver involvement. RESULTS: In patients with cancer, antipyrine clearance (0.472 +/- 0.177 ml/min/kg) was similar to that in healthy volunteers (0.456 +/- 0.198 ml/min/kg) and significantly higher than in those with cirrhosis (0.259 +/- 0.17 ml/min/kg, P less than 0.001). There was no difference in antipyrine pharmacokinetics between Class A and B involvement. In the entire population, antipyrine clearance was correlated with serum albumin levels (r = 0.294, P = 0.0002) and prothrombin activity (r = 0.416, P = 0.001). This positive correlation was not present when only the neoplastic group was considered. No correlation was found between antipyrine clearance and alkaline phosphatase levels. In patients with cancer, no relationship was found between antipyrine clearance and carcinoembryonic antigen and lactic dehydrogenase levels. CONCLUSIONS: These results show that patients with livers largely replaced by solid metastases are able to metabolize antipyrine to the same extent as healthy subjects.
Subject(s)
Antipyrine/pharmacokinetics , Colorectal Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Adult , Aged , Female , Humans , Liver Cirrhosis/metabolism , Liver Function Tests , Male , Middle AgedABSTRACT
We report a case of allergic reaction to oral 6-methyl-prednisolone in a patient with Henoch Schöenlein syndrome. When this syndrome was first diagnosed the patient was started on 6-methyl-prednisolone orally and after 4 days he developed a pruriginous generalized maculo-papular eruption. The rash disappeared 1 week after withdrawal of 6-methyl-prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6-methyl-prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivascular infiltrate of lymphocytes, histiocytes and eosinophils.