Biomedical subjects

D Skarlos

Publications and source records attributed to D Skarlos.

At least 37 records · Page 2Linked to original sources

PubMed2001

Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer. A Hellenic Cooperative Oncology Group phase II study.

AIM: To evaluate the activity and acute toxicity of the combination of weekly paclitaxel as first-line chemotherapy and trastuzumab, in patients with HER-2/neu overexpressing advanced breast cancer (ABC). BACKGROUND: Weekly paclitaxel has been shown to be a well tolerated treatment with considerable activity in patients with ABC. Clinical trials with transtuzumab, a humanized anti-p185 HER-2/neu monoclonal antibody have demonstrated that this agent produces objective responses in patients with ABC. PATIENTS AND METHODS: From December 1998 to April 2000, 34 patients with HER-2/neu overexpressing ABC were treated with weekly paclitaxel; given by one-hour infusion at a dose of 90 mg/m2 immediately followed by trastuzumab, 4 mg/kg as a loading dose and 2 mg/kg i.v. given over 30 min, thereafter weekly for at least 12 weeks. Expression of HER-2/neu was determined by immunohistochemical analysis on fixed, paraffin-embedded tissues. Eligible patients were required to have > or = 25% stained tumor cells. RESULTS: Thirty-three patients completed at least 12 weeks of combined treatment. After completion of the 12th week of treatment, four patients (12%) achieved complete and 17 (50%) partial response. Median duration of response was 11.6 months. More frequent side effects included anemia (56%). neutropenia (27%), peripheral neuropathy (78%), diarrhea (30%), alopecia (70%), arthralgias/myalgias (62%), fatigue (59%) and hypersensitivity reactions (62%). Median time to progression was nine months while median survival had not been reached CONCLUSIONS: The combination of weekly paclitaxel and trastuzumab is a safe and active regimen for patients with HER-2/neu overexpressing ABC. Randomized phase III studies with this combination are warranted.

Adult↗

PubMed2001

Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF in high-risk breast cancer.

Dose-dense sequential chemotherapy appears to be a promising approach in the management of patients with operable breast cancer. We evaluated the tolerability of such a novel chemotherapeutic regimen in high-risk patients. From February 1995 until September 1997, 49 women with histologically confirmed breast cancer and > or =10 involved axillary nodes were treated postoperatively with three cycles of epirubicin (110 mg/m(2)) followed by three cycles of paclitaxel (250 mg/m(2) in a 3-hour infusion) followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m(2), methotrexate 57 mg/m(2), fluorouracil 840 mg/m(2); E-T-CMF). All cycles were repeated every 2 weeks with G-CSF support. Ovarian ablation with monthly injections of triptorelin for 1 year was performed in premenopausal patients and tamoxifen was prescribed for 5 years to all women with positive receptor status after the completion of chemotherapy. A total of 456 cycles of chemotherapy were administered, 363 (80%) of them at full dose. Forty-seven (96%) patients received all 9 cycles of chemotherapy. Relative dose intensity of epirubicin was 0.98, of paclitaxel 0.97, of cyclophosphamide 0.99, of methotrexate 0.98 and of fluorouracil 0.99. Grade 3--4 toxicities included anemia (8%), leukopenia (8%), peripheral neuropathy (6%), neutropenia (4%), thrombocytopenia (4%), stomatitis (2%), diarrhea (2%), fatigue (2%) and hypersensitivity reaction (2%). Febrile neutropenia occurred in 2 patients. Alopecia was universal. After a median follow-up of 3 years, 11 women (22%) relapsed and 4 (8%) died. The 3-year actuarial disease-free survival rate was 72% and the 3-year overall survival rate 90%. The E-T-CMF regimen is well tolerated, as adjuvant treatment, in patients with operable breast cancer with promising activity and deserves further evaluation in phase III studies.

Adult↗

PubMed2000

BRCA1 mutation analysis in breast/ovarian cancer families from Greece.

Germline mutations in BRCA1 gene account for varying proportions of breast/ovarian cancer families, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. We have screened for mutations the entire coding sequence of BRCA1 in 30 breast/ovarian cancer women with family history of two or more cases of breast cancer under age 50 and/or ovarian cancer at any age. Genomic DNA from patient was initially analyzed for truncating mutations in exon 11 with PTT followed by DNA sequencing. In the cases where no frameshift mutation was observed in exon 11, all other exons were screened with direct sequencing. Two novel (3099delT, 3277insG) and three already described (3741insA, 1623del5-TTAAA, 5382insC-twice) truncating mutations were identified. In addition, 6 point mutations (L771L, P871L, E1038G, K1183R, S1436S, S1613G) which are already classified as polymorphisms were identified. Three unclassified intronic variants (IVS16-68 G>A, IVS16-92 G>A, IVS18+65G>A) were also detected. These results show that BRCA1 deleterious mutations are present in a fraction (20%) of Greek breast/ovarian cancer families similar to other European countries. Mutations were detected in high- (>/=3 members) as well as in moderate-risk (2 members) families. This is the first report of BRCA1 mutation analysis in Greece.

Adult↗

PubMed2000

Phase II study of temozolomide in patients with relapsing high grade glioma and poor performance status.

Temozolomide (SCHS2.365), an oral alkylating agent which penetrates the blood-brain barrier, evolved as an alternative to dacarbazine. The aim of this study was to evaluate the efficacy and safety of temozolomide in terms of overall survival, progression-free survival, clinical benefit and health related quality of life in symptomatic patients with relapsing malignant glioma and a poor performance status. Eleven patients were enrolled in the study. The median age was 44.6 years. Patients were treated with temozolomide per os at a dose of 150-200 mg/m2 daily for 5 consecutive days. Each cycle was repeated every 28 days. The median number of courses given per patient was 3.5. Nine patients were assessable for response. All patients were evaluable for toxicity. Based on radiographic findings 4 patients had stable disease (2 patients after a total of 16 cycles, and 2 patients after a total of 10 cycles). Four patients had progressive disease after 2 to 4 cycles. Of these 3 patients demonstrated a clinical benefit and one patient died after 3 cycles of treatment. Six patients had a significant clinical benefit even after 2 cycles of treatment with improvement of their neurological and performance status. Hematologic toxicity Gr II-III occurred in 3/9 patients. Nonhematologic toxicity consisted of Gr I nausea, and vomiting. In conclusion temozolomide appears to be a useful alternative for patients with relapsing malignant glioma after radiation and surgery and a poor performance status with little or no toxicity and considerable clinical benefit.

Adult↗

PubMed2000

Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): a multicenter randomized trial. Hellenic Cooperative Oncology Group (HeCOG).

PURPOSE: The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity, reasonable activity and easy outpatient administration. Purpose of our present prospective study was to evaluate the dose response relationship of paclitaxel. PATIENTS AND METHODS: Since July 1996, 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial. Ninety nine patients (group A) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 (group B) to receive the same regimen with paclitaxel increased to 225 mg/m2. Eligibility criteria included WHO performance status 0-2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis, no prior chemotherapy and adequate renal and hepatic function. Patients in both groups were well-matched with baseline disease characteristics. RESULTS: In group A with 90 evaluable patients, the response rate was 25.6% (6 CR, 17 PR) whereas in group B with 88 evaluable patients, the response rate was 31.8% (3 CR, 25 PR), P = 0.733. Median time to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months, P = 0.044). The median survival was 9.5 months for group A versus 11.4 months for group B (P = 0.16). The one-year survival was 37% for group A and 44% for group B (P = 0.35). The best prognostic factor for one-year survival was the response rate (P < 0.0001). With a relative dose intensity of paclitaxel 0.94 in both groups, neurotoxicity (P = 0.025) and leucopenia (P = 0.038) were more pronounced in group B patients. No toxic death was observed. CONCLUSIONS: Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia. The better response rate, the longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant.

Adult↗

PubMed2000

Second-line chemotherapy with weekly oxaliplatin and high-dose 5-fluorouracil with folinic acid in metastatic colorectal carcinoma: a Hellenic Cooperative Oncology Group (HeCOG) phase II feasibility study.

BACKGROUND: Oxaliplatin is a novel platinum derivative, which, combined with 5-fluorouracil (5-FU), and folinic acid (FA), demonstrates synergistic activity in metastatic colorectal cancer (MCC). The HeCOG performed a multicenter phase II study of a weekly oxaliplatin administration schedule in patients with previously treated MCC to evaluate the antitumor efficacy and toxicity of this combination. PATIENTS AND METHODS: Eligible patients included those who relapsed after or during chemotherapy with 5-FU and FA and/or irinotecan. Prior radiotherapy was accepted provided that measurable disease was outside the radiation fields. Other eligibility criteria included written informed consent, a WHO performance status < or = 2 and adequate bone marrow, liver and renal function. Treatment consisted of Oxaliplatin 50 mg/m2 by two-hour intravenous (i.v.) infusion followed by FA 500 mg/m2 (two-hour i.v. infusion) and 5-FU 2,500 mg/m2 (24-hour continuous i.v. infusion) on days 1, 8, 15, 22, 29, 36. The regimen was repeated every 50 days. RESULTS: Thirty-two patients (Median age 61 years, range 25-76) entered the trial. The majority (75%) had progressed after receiving first-line chemotherapy. Diarrhea was the main non-hematologic toxicity. More than half of the patients (53%) developed grades 3 or 4 diarrhea. Due to this side effect only 29% of cycles were given with at least 90% of the planned dose of 5-FU. Hematologic toxicity included grade 3 neutropenia and thrombocytopenia (10% for each), and grade 4 thrombocytopenia (3%). Two patients (6%) died of sepsis, one related to neutropenia and one due to urinary tract sepsis. Sixteen patients (50%) developed grades 1 and 2 neurotoxicity in the form of sensory neuropathy, which was mild and transient. The objective response rate was 13% (95% CI: 3%-29%). All four responses were partial. Twelve patients (38%) had stable disease and 8 (25%) progressive disease. The median time to progression was three months and the median survival was nine months from the start of therapy. The Kaplan-Meier estimated probability of one-year survival for the group as a whole was 32%. CONCLUSIONS: The weekly administration of oxaliplatin with 5-FU and FA was associated with considerably less neurotoxicity than other schedules. However, the high percentage of diarrhea suggests that a dose reduction of 5-FU in this regimen may result in better therapeutic synergy.

Adenocarcinoma↗

PubMed2000

Phase II study of pegylated liposomal doxorubicin: inactive in recurrent small-cell lung cancer. A Hellenic Cooperative Oncology Group Study.

PURPOSE: Although clinical experience with liposomal doxorubicin is still limited in solid tumours, single agent Caelyx (pegylated liposomal doxorubicin) treatment has shown promising results in AIDS-related Kaposi's sarcoma, metastatic breast and ovarian cancer and anecdotally in other solid tumours. This is the first report of its use in small-cell lung cancer (SCLC). The objective of this multicenter phase II study was to evaluate the safety, tolerance and anti-tumour activity of Caelyx as monotherapy in patients with recurrent SCLC. PATIENTS AND METHODS: A total of 14 patients with recurrent SCLC who had not received prior treatment with doxorubicin, were accrued into this phase II study. All patients had progressed or relapsed after first-line chemotherapy. All but one had achieved objective responses to first-line treatment with median duration of five months (range 2-18 months) but half of them had experienced 'refractory' relapses (within 3-4 months). Study treatment consisted of Caelyx 50 mg/m2 (1-hour i.v infusion every 4 weeks for 6 cycles). RESULTS: No responses were seen but in three patients disease was stabilised for a median of three months. The median number of cycles was 2 per patient, with 11 of 14 patients not completing 6 cycles of Caelyx treatment. From those, five patients were removed from the study after only one cycle due to rapid disease progression, and one was withdrawn after three cycles due to prolonged toxicity. Overall, treatment was well tolerated with no episodes of grade 4 toxicity and only two episodes of grade 3 toxicities: one of thrombocytopenia and one of prolonged palmar-plantar erythrodysesthesia (PPE). CONCLUSIONS: These results demonstrate limited activity of Caelyx in this patient population, which may be related to the poor prognostic features of such patients. Our findings are in agreement with previous observations that doxorubicin-containing combinations are rarely active in platinum/etoposide failures. However, as in other studies the favourable toxicity profile of Caelyx is confirmed.

Aged↗

PubMed2000

Combined treatment with low-dose interferon plus vinblastine is associated with less toxicity than conventional interferon monotherapy in patients with metastatic renal cell carcinoma.

The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.

Adult↗

PubMed2000

Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-alpha and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer. PURPOSE: To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer. PATIENTS AND METHODS: From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m(2)/week x 6, followed by a 2-week rest) and LV (500 mg/m(2)/week x 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients). RESULTS: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received > or =80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3-4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths. CONCLUSIONS: The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer.

Adult↗

PubMed2000

Anthracycline-based chemotherapy of primary non-Hodgkin's lymphoma of the testis: the hellenic cooperative oncology group experience.

Testicular non-Hodgkin's lymphoma is an uncommon disease and its outcome following chemotherapy and/or radiotherapy has been variable. A retrospective analysis was performed on 26 patients with primary testicular lymphoma treated predominantly with anthracycline-based chemotherapy between 1984 and 1999. The patients' median age was 60 years (range 19-82 years) with 17 (65.4%) patients being older than 60 years. Four (15.4%) patients had constitutional B symptoms. There were 11 (42.3%) patients with high grade lymphoma, 12 (46.2%) with intermediate grade, 1 (3.8%) with low grade and 2 (7.7%) were not classified. According to the Ann-Anbor staging system, 18 patients (69.2%) had early (stage I/II) and 8 (30.8%) advanced (stage III/IV) disease. Chemotherapy was administered to 24 patients including 22 patients who received anthracycline-based chemotherapy. Two stage IEA patients were treated with orchidectomy and adjuvant radiotherapy to the regional lymph nodes without systemic chemotherapy. Chemotherapy alone resulted in a complete remission (CR) in 14 (58.3%) of 24 patients and partial remission in 1 (4.2%), amounting to an overall response rate (RR) of 62.5%. Of the 5 stage I patients who had chemotherapy on an adjuvant basis, 4 (80%) had CR/no evidence of disease. Of the 11 stage II patients, 8 (72.7%) achieved CR and 1 (9.1%) PR (overall RR of 81.8%). CR was obtained in 2 (25%) of 8 stage III/IV patients. Both patients remain disease free for 26 and 65 months. Excluding the 5 stage I patients, chemotherapy resulted in a CR in 10/19 (52.6%) patients and a PR in 1/19 (5.2%), inducing an overall RR of 57.8%. The mean duration of response was 75 months (range 8-145.5+ months). After a median follow-up of 87 months (range 0.13-145.5+ months) the median survival time was 31 months (range 0.13-145.5+ months) and the median time to progression (TTP) 17 months (range 0.13-145.5+ months). The median TTP was significantly higher in early disease compared to that of advanced disease (52 vs. 3 months, p = 0.02). Of the 3 patients who relapsed following disease-free status, CNS involvement occurred in 2 stage II patients and contralateral testis involvement in 1 stage IEA, respectively. The latter remained disease free for 2 years following orchidectomy alone. The other 2 patients who relapsed did not respond to salvage chemotherapy and died. There was no significant relationship between the values of LDH and beta(2)-microglobulin with the outcome except for ESR which was significantly related with the CR (p = 0.005) or RR (p = 0.005). In conclusion, patients with primary testicular lymphoma have a poor outcome, despite the treatment with anthracycline-containing regimens. Treatment with anthracycline-based chemotherapy is recommended in patients at early stages. In advanced disease, more intensive or investigational regimens should be considered. Because the relapse rate in the CNS and contralateral testis is quite high in most studies, prophylactic CNS treatment and radiotherapy to the other testis should be included in the management of testicular lymphoma.

Adult↗

PubMed2000

Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study.

PURPOSE: To evaluate the efficacy of the carboplatin/paclitaxel combination in patients with carcinoma of unknown primary site (CUP). PATIENTS AND METHODS: Seventy-seven consecutive CUP patients (45 women and 32 men; median age, 60 years) were treated with carboplatin at target area under the curve 6 mg/mL/min followed by paclitaxel 200 mg/m(2) as a 3-hour infusion and granulocyte colony-stimulating factor from days 5 to 12. Treatment courses were repeated every 3 weeks to a maximum of eight cycles. Forty-seven patients had adenocarcinomas, 27 had undifferentiated carcinomas, and three had squamous cell carcinomas. Thirty-three patients presented with liver, bone, or multiple organ metastases, 23 with predominantly nodal/pleural disease, and 19 (16 women) with peritoneal carcinomatosis. RESULTS: The overall response rate by intent-to-treat analysis was 38.7% (95% confidence interval, 27.5% to 49.9%). There were no differences in response between adenocarcinomas and undifferentiated carcinomas, but efficacy varied among clinical subsets. The response rates and median survival times in the three clinically defined subsets were 47.8% and 13 months, respectively, for patients with predominantly nodal/pleural disease, 68.4% and 15 months, respectively, in women with peritoneal carcinomatosis, and 15.1% and 10 months, respectively, in patients with visceral or disseminated metastases. Chemotherapy was well-tolerated. CONCLUSION: Carboplatin plus paclitaxel combination chemotherapy is effective in patients with predominantly nodal/pleural metastases of unknown primary carcinoma and in women with peritoneal carcinomatosis. However, in patients with liver, bone, or multiple organ involvement, the combination offers limited benefit. The investigation of novel treatment approaches is highly warranted for this group of patients.

Adenocarcinoma↗

PubMed2000

Combination chemotherapy with paclitaxel plus carboplatin versus paclitaxel plus gemcitabine in inoperable non-small cell lung cancer: a phase III randomized study. Preliminary results. Hellenic Cooperative Oncology Group.

Gemcitabine plus paclitaxel and paclitaxel plus carboplatin are active and well tolerated in patients with advanced non-small cell lung cancer, showing similar rates of response and survival. The Hellenic Cooperative Oncology Group conducted a randomized phase III trial comparing gemcitabine plus paclitaxel with paclitaxel plus carboplatin. Patients were randomly assigned to two groups. Group A received paclitaxel 200 mg/m2 plus carboplatin (area under the curve = 6) on day I. Group B received paclitaxel in identical fashion to group A plus gemcitabine 1,000 mg/m2 on days I and 8 every 3 weeks. A minimum of two cycles and a maximum of six cycles was allowed. To date, 127 eligible patients (63 in group A and 64 in group B) have been randomized; the median follow-up time is 4.6 months. Preliminary results suggest that both combinations can be given in full doses and are well tolerated. Grade 3/4 neutropenia was mild but more prominent in group A (10% v 3%, respectively) while thrombocytopenia was not significant for either group. Moreover, severe neurotoxicity, hepatotoxicity, or cardiac toxicity has not been observed in the vast majority of patients in either group. Although patients in group B experienced higher response rates (37.5%) than those in group A (21.8%), the difference between the groups was not statistically significant. Definite conclusions about this study cannot be made until more data are available.

Adult↗

PubMed1999

Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group.

BACKGROUND: Randomized studies have shown that postoperative chemotherapy with or without radiation therapy (RT) improved local control and survival of patients with stages II or III rectal cancer. However, the optimal sequence of treatments and the optimal chemotherapeutic regimen have not been defined. Modulation of fluorouracil (FU) by leucovorin (LV) has yielded a highly significant difference in response rate from that of FU monotherapy, as suggested by an overview of randomized trials in patients with advanced colorectal cancer. However, this difference in response rate did not translate into a survival benefit. PURPOSE: To evaluate the impact on the disease-free survival (DFS) and overall survival (OS) of patients with stages II or III rectal cancer of postoperative RT and concomitant bolus FU administration alone or with additional chemotherapy using FU and high-dose LV. PATIENTS AND METHODS: From October 1989 until February 1997, 220 patients were randomized postoperatively to receive either one cycle of chemotherapy with FU (600 mg/m2/week x 6 followed by a two-week rest) and leucovorin (LV, 500 mg/m2/week x 6 as a two-hour infusion) followed by pelvic RT with concomitant FU (400 mg/m2) as a rapid intravenous injection during the first three and last three days of RT, and three more cycles of the same chemotherapy with FU and LV (standard, group A, 111 patients) or pelvic RT with concomitant FU only (experimental, group B, 109 patients). RESULTS: As of August 1998, after a median follow-up of 4.9 years, there was no significant difference in either three-year DFS (Group A, 70.3%; group B, 68.2%, P = 0.53) or OS (group A, 77%; group B, 73.3%. P = 0.75). Cox multivariate analysis revealed stage of disease, number of infiltrated nodes, tumor grade, presence of regional implants and perforation to be significant prognostic factors. The incidence of severe side effects was significantly higher in the patients in group A than in those in group B (32.4% vs. 4.6%, P < 0.0001). CONCLUSIONS: The incorporation of additional chemotherapy with FU and LV into postoperative concomitant RT and bolus infusion of FU does not offer a > or = 10% three-year survival benefit over that of concomitant RT and bolus infusion of FU, and significantly increases toxicity in patients with stages II or III rectal cancer.

Adult↗

PubMed1999

Carboplatin, methotrexate and 5-fluorouracil in combination with medroxyprogesterone acetate (JMF-M) in the treatment of advanced or recurrent endometrial carcinoma: A Hellenic cooperative oncology group study.

Twenty-three patients with advanced or recurrent endometrial carcinoma entered a prospective study of chemotherapy which consisted of carboplatin (300 mg/m2), methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3-weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg daily, p. o., until progression (JMF-M regimen). None had received prior chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had received radiotherapy. Response to treatment was evaluated every two courses. Objective response was seen in 17 of the 23 patients (74%, 95% confidence interval = 52-90%), with 2 long-lasting complete responses (9%). The median response duration was 10+ months (3-45+). The median survival was 16+ months (2-45+). The 2 complete responders, the first in the lung and the second in groin nodes, are without evidence or recurrence after 32 and 45 months, respectively. The regimen was given on an outpatient basis and was well tolerated. The major toxic effects were myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation treatment with MPA was discontinued because of thromboplebitis. In conclusion, the JMF-M regimen is highly active with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

Adult↗

PubMed1999

Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience.

Extragonadal germ cell tumours (EGCT) are uncommon, most frequently arise in the mediastinum and retroperitoneum and have variable responses to platinum-based chemotherapy. A retrospective analysis was performed on 38 patients with EGCT treated with cisplatin-based (CDDP) or carboplatin-based (CBDCA) chemotherapy between 1984 and 1998. Twenty-four patients had nonseminomatous germ cell tumours (NSGCT) and 14 seminoma. Twenty-two tumours arose in the mediastinum (13 nonseminomas, 9 seminomas) and 16 in the retroperitoneum (11 NSGCT, 5 seminomas). Initial surgery included complete resection in 1 patient, biopsy in 27 patients and debulking surgery in 10 patients. Complete response rates with chemotherapy +/- surgery were as follows: mediastinum 14 of 21 (66.66%) patients (8 of 12-75% NSGCT, 6 of 9-66.66% seminomas) and retroperitoneum 14 of 16 (87.5%) patients (9 of 11-81.81% NSGCT, 5 of 5-100% seminomas). One patient who underwent complete resection of a mediastinal malignant teratoma combined, received PVB chemotherapy on an adjuvant basis and remains alive and disease-free. Three additional seminoma patients who achieved partial response after chemotherapy remain alive and disease-free following mediastinal radiotherapy. All 14 patients with extragonadal seminomas remain alive with no evidence of disease at a median follow-up of 49 months (range 7-164), giving an overall survival of 100%. Nine of 13 (69.23%) patients with mediastinal NSGCT are long-term disease-free at a median follow-up of 43.5 months (range 7-152). Nine of 11 (81.81%) patients with retroperitoneal NSGCT remain alive and disease-free at a median follow-up of 56 months (range 14-110). Complete surgical resection of residual mass was undertaken in 10 patients (3 seminomas, 7 nonseminomas). The histology revealed necrosis/fibrosis in 6 patients (3 seminomas, 3 NSGCT) and viable cancer in 4 patients. Patients who had viable malignant cells in the resected specimens received two more courses of VelP chemotherapy. None of our patients had relapsed at the time of this analysis. None of our 6 patients who underwent testicular biopsy (1 patient) or orchiectomy (5 patients) due to suspicious ultrasound of the testis were found to have testicular tumour or fibrotic scar. In conclusion, this retrospective analysis showed significant responses in patients with either mediastinal or retroperitoneal NSGCT treated with CDDP- or CBDCA-based chemotherapy +/- surgery. All patients with extragonadal seminomas remain alive with no evidence of disease, regardless of the site at presentation.

Adolescent↗

PubMed1999

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

Adult↗

PubMed1998

Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide.

Integrins are cell-surface glycoproteins found in different forms on all cells except erythrocytes. Integrins bind to cell adhesion molecules and to proteins found in the extracellular matrix. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins which are expressed on tumour cells and are responsible for tumour invasion and metastasis. A synthetic decapeptide designated alpha P2 containing two RGD sequences radiolabelled with technetium-99m was used to image malignant melanoma in vivo. Fourteen patients previously diagnosed with metastatic melanoma underwent gamma camera imaging 20-180 min following intravenous administration of the radiolabelled synthetic decapeptide alpha P2. Six out of eight (6/8) of the lymph node metastases (75%) and all other neoplastic sites (11 sites) were successfully imaged, with the exception of three sites in the mediastinal area which were not positively imaged. In two cases there was false positive uptake in the rounded pigmented areolar/nipple area. In three cases (seven sites) the peptide scan confirmed the absence of disease in suspected lesions (true-negative). The synthetic peptide was rapidly removed from the circulation by filtration through the kidneys and excretion in the urine. No toxicity or adverse events were recorded. Radiolabelled alpha P2 peptide, which binds specifically to adhesion molecules on tumours, can be used for the in vivo detection of neoplastic metastases.

Adult↗

PubMed1998

First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): a phase II study conducted by the Hellenic Cooperative Oncology Group.

PURPOSE: To evaluate the activity and toxicity of the combination of paclitaxel given by three-hour infusion, and carboplatin as first-line chemotherapy in patients with advanced breast cancer (ABC). BACKGROUND: Paclitaxel is an active agent in ABC. Furthermore, our group has shown that the combination of paclitaxel and carboplatin is effective in anthracycline-resistant ABC. PATIENTS AND METHODS: From January 1996 until March 1997, 66 women with ABC were treated with paclitaxel (175 mg/m2) by three-hour infusion followed by carboplatin at an AUC of 6 mg x min/ml every three weeks. The median age of the patients was 56 years (range 28-75). A total of 39 patients had received adjuvant chemotherapy and 22 of them were treated with an anthracycline or mitoxantrone-containing regimen. RESULTS: A total of 324 cycles (median: six) were administered, 273 (85%) of them at full dose. The median number of delivered cycles was six. The median delivered dose intensity (DI) of paclitaxel was 55.1 mg/m2/week (range 30.5-69.3) and the relative DI was 0.95 (range 0.5-1.2). Eight patients (12%, 95% confidence interval (CI): 5%-22%) achieved complete and 28 (42%, 95% CI: 30%-55%) partial responses. Grade 3-4 toxicities included anemia (5%), granulocytopenia (24%), thrombocytopenia, nausea/vomiting and allergic reaction (3% each), myalgias/arthralgias and neurotoxicity (1.5% each). Febrile neutropenia occurred in eight (12%) patients. Alopecia was universal. After a median follow-up of 17.3 (range 0.07-24.5) months, 48 (72%) patients have demonstrated tumor progression and 24 (36%) have died. Median time to progression was 8.6 (range 0.07-23+) months and median survival 20.4 (range 0.07-24.5+) months. CONCLUSIONS: The combination of paclitaxel and carboplatin has moderate activity in ABC and can be easily delivered on an outpatient basis with manageable toxicity. This regimen may be useful especially in patients to whom anthracyclines or cisplatin administration is precluded because of other concomitant diseases.

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