Biomedical subjects

G Fountzilas

Publications and source records attributed to G Fountzilas.

At least 163 records · Page 9Linked to original sources

PubMedDate not supplied

Multidisciplinary approach to the treatment of locally and regionally advanced non-small cell lung cancer: University of Miami experience.

An intensive multimodality therapy protocol incorporating neoadjuvant chemotherapy was initiated in July 1985 for patients with either borderline resectable or unresectable non-small cell carcinoma of the lung. Thirty-five patients, 21 men and 14 women were entered till March 1991. The median age was 58 years (27-74). Histology was squamous in 15, adenocarcinoma in 11, large cell in 6, and adenosquamous carcinoma in 3. Initial stages were IIIA in 19 patients, IIIB in 14 and II in 2. All patients tolerated preoperative chemotherapy with 5-FU, etoposide and cisplatin (FED). The response to chemotherapy was complete response in 2 (6%), and partial response in 22 (63%). Thirty-two patients underwent surgery. 26 patients were rendered disease free including two found disease free at surgery. Fifteen underwent pneumonectomy, 14 lobectomy and 3 biopsy only. Interstitial radiation therapy was used in 7 patients. The median survival of all patients was 19 months, those who underwent incomplete surgical resection was 12 months and patients rendered disease free at operation 21 months. Thirteen patients are alive and free of disease, including 6 patients alive longer than 5 years. Only patients who responded to chemotherapy and also had complete resection survived more than 2 years. Aggressive neoadjuvant therapy with FED, followed by resection, brachytherapy, postoperative radiation therapy, and adjuvant chemotherapy can be safely accomplished with encouraging survival in stage III patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Subcutaneous low doses of interleukin-2 and recombinant interferon alpha with carboplatin and vinblastine in patients with advanced melanoma.

Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-alpha) with chemotherapy consisting of four cycles of carboplatin (300 mg/m2, day 1) and vinblastine (6 mg/m2, day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 x 10(6) U twice daily on days 3-6 and days 21-24 of each cycle; IFN-alpha dose was 4.5 x 10(6) U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1-14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3-4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is concluded that the CV-IL-IF regimen has limited activity and moderate toxicity.

Adult↗

PubMedDate not supplied

Diffuse large cell lymphomas: identification of prognostic factors and validation of the International Non-Hodgkin's Lymphoma Prognostic Index. A Hellenic Cooperative Oncology Group Study.

Several clinical prognostic factors have been identified that predict treatment outcome in patients with diffuse large cell lymphomas. An International Non-Hodgkin's Lymphoma Prognostic Index (IPI) has been recently formulated. We tried to identify the clinical prognostic factors that predict treatment outcome in Greek patients with diffuse large cell lymphomas and validated the IPI in these patients. The possible prognostic variables for tumor response, relapse-free (RFS) and overall survival (OS) were analyzed in 239 consecutive patients treated with anthracycline-based chemotherapy regimens. In univariate analysis, factors associated with poor response were stages III-IV, performance status (PS) >/=2, spleen and bone marrow involvement, more than one extranodal site involved, increased lactate dehydrogenase (LDH) value, hemoglobin (Hb) <12 g/dl, albumin <3.5 g/dl, erythrocyte sedimentation rate (ESR) >50 mm/h. Multivariate analysis identified stage, PS, more than one extranodal site involved, increased LDH level, and ESR > 50 mm/h as the factors more predictive of poor response. For RFS, multiple Cox analysis found stages III-IV and bone marrow involvement to be statistically significant. For OS, multiple Cox analysis identified stage III-IV, PS >/=2, bone marrow involvement, more than one extranodal site involved, increased LDH level and ESR > 50 mm/h as negative prognostic factors. Patients stratified in the different risk groups of the IPI had a significantly different outcome regarding complete response (CR) rate, RFS and OS. In conclusion, although age >60 years was not recognized as an adverse factor in this analysis, our patients stratified in the different groups of the IPI had significant differences in CR rate, 2-year RFS and OS verifying the prognostic significance of the index. Bone marrow involvement and ESR > 50 mm/h, parameters that are not included in the IPI, adversely affected survival.

Adult↗

PubMedDate not supplied

Combination regimen with carboplatin, epirubicin and etoposide in metastatic carcinomas of unknown primary site: A Hellenic Co-Operative Oncology Group Phase II Study.

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial. Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m2 IV D1, epirubicin 45 mg/m2 IV D1 and etoposide 120 mg/m2 IV D1-3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95% CI 25-49%). An equal activity of the regimen was observed between the two major histopathological types, the pdc and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively nontoxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.

Adult↗

PubMedDate not supplied

Dose-dense adjuvant chemotherapy with epirubicin monotherapy in patients with operable breast cancer and >/=10 positive axillary lymph nodes. A feasibility study.

Forty-one patients with operable breast cancer and >/=10 positive axillary lymph nodes were treated with 6 cycles of dose-dense adjuvant chemotherapy consisting of epirubicin (100 mg/m2) every 2 weeks with G-CSF support. A total of 240 cycles were administered, all of them at full dose and 19 (8%) with a delay. Thirty-eight (93%) patients completed the treatment according to the protocol. The relative dose intensity of epirubicin was 0.99. Grade 3 toxicities included anemia (3%), nausea and vomiting (5%) and alopecia (71%). After a median follow-up of 40 months, 16 (39%) patients were free of relapse. In conclusion, the present study has shown that the administration of dose-dense chemotherapy with epirubicin is feasible in the adjuvant setting with minimal toxicity.

Adult↗

PubMedDate not supplied

A randomized comparative study of antiemetic prophylaxis with ondansentron in a single 32-mg loading dose versus 8 mg every 6 h in patients undergoing cisplatin-based chemotherapy.

In several studies a single dose of 32 mg was compared to an ondansentron (OND) administration schedule of every 6 h, yielding no differences in overall efficacy. The aim of this randomized comparative study was to identify differences of these two schedules on an hour-to-hour control of nausea and vomiting, during the first 24 h in patients receiving cisplatin (CDDP)-based chemotherapy. One hundred ten patients were randomly assigned to two groups (A and B); all received combination chemotherapy with CDDP at a dose of 100 mg/m2. OND was administered as follows: group A: 8 mg, 30 min before the infusion of CDDP, and repeated every 6 h after the first dose (totally 4 doses) in the first 24 h, and group B: 32 mg before CDDP, as a loading dose and this was the total dose for the first 24 h. No overall difference was noticed during the first 24 h, as well as the next 3 days from the infusion of CDDP in the intensity of vomits, vomits without gastric content (retches), and nausea. In a more detailed monitoring of the distribution of emetic episodes during the first 24 h, there were important differences between these two antiemetic schedules: for group A an increased vomiting with or without gastric content between midnight and 6 p.m. was observed, and for group B between 6 p.m. and midnight (vomits with p 0.03, and without gastric content p 0.02). Preloading with the total 24-hour dose of OND 32 mg exhibits a more potent antiemetic activity during the initial 18 h, becoming weaker over the last 5 h of the first day, whereas the every-6-hour schedule leaves periods of poor emesis control between dosing intervals.

Adult↗

PubMedDate not supplied

Cyclophosphamide, mitoxantrone, fluorouracil versus conventional CMF as adjuvant treatment in node-positive breast cancer patients. A Hellenic Cooperative Oncology Group Study.

362 evaluable node-positive patients with stage II breast cancer were randomized, receiving either 6 cycles of conventional CMF or 6 cycles of the combination of cyclophosphamide (500 mg/m2), mitoxantrone (Novantrone 10 mg/m2), and fluorouracil (500 mg/m2; CNF). After a median follow-up of 51 months, 64 (36%) patients relapsed in the CMF group and 60 (33%) in the CNF group (p=0.8276). By Cox multivariate analysis, tumor size, menopausal status and number of involved nodes were retained as independently significant variables. Toxicities were remarkably similar in both groups. It appears that after a median follow-up of 51 months there is no significant difference in relapse-free survival between node-positive patients with breast cancer who received either 6 cycles of the conventional CMF or the CNF combination as adjuvant treatment.

Adult↗

PubMedDate not supplied

Phase II study of 5-fluorouracil and interferon-gamma in patients with metastatic colorectal cancer. A Hellenic Cooperative Oncology Group Study.

Preclinical data have shown a synergism between 5-fluorouracil and interferon-gamma against human colon carcinoma cell lines. We conducted a phase II trial of this combination in 34 patients with metastatic colorectal cancer. 5-Fluorouracil was administered as an intravenous bolus of 500 mg/m2 weekly and interferon-gamma subcutaneous injection at a dose of 200 micrograms (6 x 10(6) IU) 3 times a week. Thirty-two patients were evaluable for response. There was one complete and two partial responses (response rate 9.0%, 95% CI 1.98-25.02%). Eleven patients (34%) had stable disease. Common toxicities included fever 81%, nausea/vomiting 19%, diarrhea 16%, flu-like syndrome 16%, malaise 12.5% and leukopenia 12.5%. These results indicate that the above combination of 5-fluorouracil and interferon-gamma has an unimpressive activity in patients with advanced colorectal carcinoma. Toxicity was very tolerable.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Haplotypes of human leukocyte antigens among patients with nasopharyngeal cancer in Greece.

The concept that the major histocompatibility complex (MHC) plays an important role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups has gained increased attention during the last 15 years. Earlier studies have suggested that an increased risk of NPC is associated with specific phenotypes of human leukocyte antigens (HLA). The present study was performed to examine the association of HLA specificities and haplotypes with NPC in a Greek population. In a genotypical study of 53 patients, a significant association between the haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the above haplotype was significantly associated with longer disease-free interval. HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell histology than among those with the undifferentiated type. These results suggest that MHC loci are probably implicated in the pathogenesis and outcome of NPC in Greek patients.

Adolescent↗

PubMedDate not supplied

A randomized open-label parallel-group study comparing ondansetron with ondansetron plus dexamethasone in patients with metastatic breast cancer receiving high-dose epirubicin. A Hellenic Cooperative Oncology Group study.

AIMS AND BACKGROUND: The purpose of this multicenter randomized, open-label, parallel-group study was to assess whether the addition of low-dose dexamethasone to ondansetron results in improved control of chemotherapy-induced emesis in patients undergoing first-line chemotherapy with high-dose epirubicin. METHODS & STUDY DESIGN: Patients were randomized to receive either 24 mg of ondansetron or 24 mg of ondansetron plus 8 mg of dexamethasone administered as an intravenous infusion 30 minutes prior to administration of chemotherapy. Both groups of patients received 8 mg of ondansetron given orally from day 2 to 5 two times daily. Fifty-three patients received ondansetron and 50 received ondansetron plus dexamethasone. The patients recorded nausea and the number of vomits and retches daily on diary cards. RESULTS: Significantly more patients in the ondansetron plus dexamethasone group experienced neither vomiting nor retching during the first day of the first course of chemotherapy compared to those receiving ondansetron alone (79.6% vs 53.8%, P = 0.0062). Furthermore, there was a trend in favor of ondansetron plus dexamethasone in the control of nausea. There was no statistically significant difference between ondansetron plus dexamethasone versus ondansetron alone in protecting patients from emesis between days 2 and 5 of the first course of chemotherapy (66.7% vs 62.7%, P = 0.68). This was probably due to the small sample size. Ondansetron was well tolerated, with 15 patients (15%) reporting adverse events such as headache or constipation. CONCLUSIONS: It appears that ondansetron given intravenously in combination with dexamethasone is more effective than ondansetron alone in the control of acute emesis in patients undergoing their first course of chemotherapy with high-dose epirubicin. No difference between the regimens was found with regard to nausea and delayed emesis control.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Radiation and concurrent carboplatin administration in locally advanced head and neck cancer. A Hellenic Cooperative Oncology Group Study.

AIMS AND BACKGROUND: To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. METHODS: Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n = 10), hypopharynx (n = 5), larynx (n = 12), oral cavity (n = 2), paranasal sinuses (n = 3), salivary glands (n = 1) and unknown (n = 1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. RESULTS: Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received > 66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). CONCLUSIONS: Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

Adult↗

PubMedDate not supplied

Accelerated bifractionated radiation with concurrent cisplatin administration in locally advanced head and neck cancer: a feasibility study.

AIMS AND BACKGROUND: To test the feasibility of accelerated interrupted twice-daily radiation and concurrent cisplatin administration in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: Nineteen patients with locally advanced head and neck cancer were treated with accelerated bifractionated radiation with concurrent administration of cisplatin. There were 18 men and 1 female with a median age of 60 years (range, 17-71) and median performance status of 90 (range, 80-100). Sixteen patients (85%) presented with stage IV disease. Primary site included the nasopharynx (n = 7), oropharynx (n = 5), hypopharynx (n = 1) and larynx (n = 6). Radiation consisted of two fractions of 1.6 Gy each daily, five times weekly to a total dose of 64 Gy. Cisplatin was administered at a dose of 100 mg/m2 on days 2 and 28 of the treatment period. RESULTS: Nine patients achieved a complete response (47%; 95% Cl, 25%-70%) and 5 a partial response (26%; 95% Cl, 7%-46%). Grade III-IV toxicity included leukopenia (16%), mucositis (26%), dry mouth (5%), weight loss (16%) and infection (5%). After a median follow-up of 27.11 months (range, 1-33 +), 9 patients have died. Median time to progression was 11 months (range, 1-32 +) and median survival 25 months (range, 1-32 +). CONCLUSIONS: Accelerated twice-daily radiation with concurrent cisplatin is effective in locally advanced head and neck cancer and can be safely given with manageable toxicity.

Adolescent↗

PubMedDate not supplied

Serum soluble interleukin-2 receptors in epithelial ovarian cancer patients.

The levels of soluble interleukin-2 receptors (sIL-R2) were measured in the serum of 52 patients with epithelial ovarian carcinoma as well as in 25 age and sex-matched normal controls. The mean serum level of sIL-R2 was increased in 37 patients (71.2%). Comparison of these levels to those of normal controls showed a highly statistically significant difference (p < 0.001). Serum sIL-R2 levels were not related to histology, clinical stage or the presence of ascites (p = 0.58, p = 0.32 and p = 0.67, respectively), nor did they follow disease activity or response to chemotherapy. However, patients with higher pretreatment sIL-2R levels (more than 1200 U/ml) were found to have a longer survival (p < 0.02), possibly explained by the presence of activated lymphocytes and a better immune surveillance. We conclude that the serum level of sIL-R2: a) is elevated in ovarian cancer patients, b) has no relationship with histological subtypes, tumor burden or the presence of ascites, c) cannot serve as a valuable tumor marker for the monitoring of patient treatment, and d) has a prognostic value for survival.

Adult↗

PubMedDate not supplied

Soluble interleukin-2 receptors in patients with advanced colorectal carcinoma.

The levels of soluble interleukin-2 receptors (sIL-2R) were measured in the serum of 52 patients with advanced colorectal carcinoma and compared to CEA and CA 19-9 levels. Twenty-five normal, age and sex-matched individuals served as controls. Seventy-five per cent of the patients had increased mean serum levels of sIL-2R (1539 +/- 155 U/ml), while normal controls had mean levels of 555 +/- 31 U/ml (p < 0.001). The relationship with hepatic or lymph nodal metastases showed no statistically significant difference (p = 0.34 and p = 0.47, respectively). Serum sIL-2R levels showed a linear correlation with CEA (p < 0.05). Patients with lower pretreatment sIL-2R levels (less than 1.200 U/ml) had a longer survival than patients with higher initial levels (more than 1.200 U/ml) (p = 0.0049). In conclusion, the present work shows that the serum levels of sIL-2R: a) are elevated in patients with advanced colorectal cancer, b) have no relationship with the type of metastases, c) correlate with serum CEA and d) have a prognostic value for survival.

Adult↗

PubMedDate not supplied

Effects on blood coagulation of adjuvant CNF (cyclophosphamide, novantrone, 5-fluorouracil) chemotherapy in stage II breast cancer patients.

We prospectively studied the alterations of coagulation during adjuvant CNF (Cyclophosphamide, Novantrone--Mitoxantrone, 5-Fluorouracil) chemotherapy in patients with stage II breast cancer. In 50 consecutive stage II breast cancer patients (pre-peri-postmenopausal), and 50 controls, serial coagulation parameters including prothrombin time (P.T.), partial thromboplastin time (P.T.T.), fibrinogen, fibrinogen/fibrin degradation products (F.D.P.), protein C, protein S, antithrombin III (AT-III) and platelet count were performed. Blood samples for coagulation tests were collected at pretherapy, midtherapy (before the 3rd course), before the 6th course of chemotherapy, and 2 months after the cessation of therapy (post-therapy) of 6 cycles of adjuvant chemotherapy (Cyclophosphamide 500 mg/m2, Novantrone 10 mg/m2, 5-Fluorouracil 500 mg/m2). Chemotherapy was repeated every 3 weeks. None of our stage II breast cancer patients receiving adjuvant CNF chemotherapy developed thromboembolic complications. Before any treatment all the tested coagulation parameters were within the normal limits as compared to controls. No statistically significant changes of FDP were noted throughout the study. Fibrinogen, plasma protein C, protein S and AT-III were significantly decreased during chemotherapy. This decline was more evident at midtherapy. Their levels returned to the pretherapy values 2 months after the completion of chemotherapy. The P.T. was statistically shortened, while the P.T.T. showed a statistically significant prolongation during chemotherapy. In conclusion, it appears that monitoring stage II breast cancer with sophisticated coagulation tests during adjuvant CNF chemotherapy can not identify patients at high risk for thromboembolic events. These serially performed coagulation tests, could be considered as a cost-intensive monitoring and not justifiable as a screening for breast cancer patients receiving adjuvant chemotherapy. However, the increasing number of reports of life-threatening and sometimes fatal thromboembolic events following chemotherapy or hormonochemotherapy are of great concern. Our results suggest caution when using chemotherapeutic agents in patients with other thrombosis risk factors, since a significant decrease of protein C and protein S was observed in all patients. Additional studies are required to determine the exact association between chemotherapy and/or hormonochemotherapy and thrombotic events.

Adult↗

PubMedDate not supplied

c-erbB-2 oncoprotein is overexpressed in poorly vascularised squamous cell carcinomas of the head and neck, but is not associated with response to cytotoxic therapy or survival.

The prognostic and predictive role of c-erbB-2 oncoprotein in human malignancies remains controversial. The pattern of expression and the biological behaviour of c-erbB-2 protein was investigated in a series of 89 locally advanced squamous carcinomas of the head and neck. Possible associations between c-erbB-2 and T,N-stage, histological grade, microvessel density and the expression of bcl-2 and p53 proteins were sought. Biopsy material had been collected prior to the initiation of treatment which consisted of platinum based induction chemotherapy or concurrent chemotherapy and radiotherapy. In all cases, follow-up of at least 2 years duration was available. Positive staining was seen in 27 out of 89 (30.4%) cases and was invariably cytoplasmic, exhibiting strong reactivity in more than 50% of tumour cells. Such c-erbB-2 overexpressing tumours were not associated with a response to radiotherapy and/or induction chemotherapy. Further, survival analysis did not disclose any difference in the overall or relapse free survival between c-erbB-2 positive and negative cases. Similarly, no relationship was found with T,N-stage, histological grade and bcl-2 or p53 expression. There was, however, a significant inverse association between c-erbB-2 expression and microvessel density (p = 0.0001). Interestingly, tumours with low vascular grade (VG; MS < 26) and positive c-erbB-2 expression were less frequently associated with local aggressiveness compared to c-erbB-2 negative tumours and low VG (5/27 vs. 12/18; p = 0.001), or to c-erbB-2 negative tumours and high VG (MS > 27) (5/27 vs. 19/44; p = 0.03). These differences were statistically significant but were not related to treatment response or prognosis. Nonetheless, when patients with highly angiogenic tumours were analysed for survival, irrespective of the c-erbB-2 status, they showed a poorer prognosis than those having a low microvessel density (p = 0.06 and 0.05 for overall and relapse free survival, respectively). Six out of 89 patients presented with distant metastases, five of which had tumours negative for c-erbB-2 expression. Our results seem to indicate that the pattern of c-erbB-2 expression in locally advanced inoperable head and neck cancer is exclusively cytoplasmic. c-erbB-2 reactivity is of little value in predicting survival or chemo-radiotherapeutic response. Expression of genes related to angiogenesis or other invasion and migration pathways are, apparently, more important.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Bax protein expression in colorectal cancer: association with p53, bcl-2 and patterns of relapse.

This study evaluated the frequency and the prognostic significance of bax, bcl-2 and p53 proteins in stage B and C adenocarcinomas of the colon and rectum. Paraffin-embedded specimens from 268 patients with colorectal adenocarcinomas, treated with surgery, were assessed; of these 160 cases were Duke's stage B and 108 cases were Duke's stage C disease. Adjuvant chemotherapy was given to all stage C and to 108 out of 160 stage B cancer patients, while those having rectal malignancy also received pelvic radiotherapy. Duke's stage B patients were treated either with surgery alone or with surgery and radiotherapy. The follow-up period at the time of analysis ranged from 12-72 months (median 32 months). Immunohistochemical expression of bax, bcl-2 and mutant p53 proteins was detected with a frequency of 42%, 37% and 48%, respectively. However, the expression was strong only in 17% of tumours, on average. A strong bcl-2 expression was significantly associated with a strong bax expression (p < 0.0001) and with absence of p53 nuclear accumulation (p < 0.005). There was, however, no correlation between bax and p53 proteins. Furthermore, bcl-2 expression was significantly more frequent in grade I and 2 adenocarcinomas compared to grade 3 disease (p = 0.01). In stage B (but not C) adenocarcinomas, bax expression was directly associated with higher risk of local relapse (p = 0.04). By contrast, cases with p53 nuclear accumulation, when they had received adjuvant radiotherapy, were significantly associated with a lower incidence of local relapse (p = 0.01), but a higher rate of distant metastasis (p = 0.06). Multivariate analysis for disease free and overall survival showed that bax expression and high Duke's stage were independent prognostic parameters associated with an unfavourable outcome (p = 0.009 and p = 0.0001, respectively). It was concluded that the immunohistochemical expression of bax is a marker of poor prognosis and of a higher risk of local relapse in patients with colorectal adenocarcinomas. p53 nuclear accumulation is associated with a better local control, following radiotherapy and with a metastatic phenotype. The development of novel monoclonal antibodies recognising specifically the mutated versus the wild type form of proteins would apparently improve the prognostic and predictive value of the immunohistochemically detected apoptotic proteins.

Adenocarcinoma↗

PubMedDate not supplied

An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group.

Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required.

Adult↗