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V Georgoulias

Publications and source records attributed to V Georgoulias.

At least 19 recordsLinked to original sources
PubMed1999

Angiogenesis vs. response after combined chemoradiotherapy of squamous cell head and neck cancer.

Oxygen/drug supply to cancer cells is an important factor defining response to radiotherapy and chemotherapy. Although tumor angiogenesis is considered an important prognostic marker, its role in the outcome of chemotherapy and radiotherapy is unknown. In the present study we examined the possible correlation of the degree of angiogenesis with response to cytotoxic therapy in locally advanced squamous cell head and neck cancer (HNC). Vascular grade (VG) was assessed immunohistochemically using the JC70 monoclonal antibody (MAb) in tumor specimens from 76 patients treated with platinum/5-fluorouracil (with or without methotrexate) induction chemotherapy (ICT) (n = 37) or concurrent chemoradiotherapy (CCRT) with cisplatin or carboplatin (n = 39). Seventeen of 76 analyzed patients had an overall microvessel score of < 11 (VGI), 25/76 of 11-30 (VG2), 16/76 of 31-50 (VG3) and 18/76 of > 50 (VG4). Complete response rate after ICT or after CCRT was higher in cases with an intermediate vascularization (VG2,3). Both local relapse-free and overall survival were significantly better in the VG2 group. Patients treated with CCRT had a better survival compared to those treated with ICT. This was mainly observed in VG1 tumors. Multivariate analysis showed that VG and treatment modality were independent prognostic factors for local relapse and survival. Intratumoral angiogenesis correlation with the cytotoxic therapy outcome is likely to follow a bell-shaped relation, the response being better in cases with an intermediate VG. This may be the consequence of 2 vasculature-dependent factors, i.e., the drug/oxygen availability and the ability of cancer cells to undergo rapid repopulation in optimally oxygenated conditions. Our pilot study stresses the importance of individualization of therapy according to VG.

Adult↗
PubMed1999

Concurrent twice-a-week docetaxel and radiotherapy: a dose escalation trial with immunological toxicity evaluation.

PURPOSE: In vitro studies show that docetaxel (Taxotere) is potent radiosensitizer. In a previous study we observed a 27% complete response rate after radiotherapy and weekly docetaxel for non-small-cell lung cancer. In this dose escalation study we investigated the feasibility of a twice-a-week docetaxel regimen together with conventionally fractionated radiotherapy for brain, chest, and pelvic tumors. METHODS AND MATERIALS: Nine patients with stage IIIb lung cancer, 9 with stage IVa pelvic tumors, and 9 with brain glioblastoma were recruited. The starting dose was 15 mg/m2 (twice a week) and was escalated by 4 mg/m2 increments every 3 patients with chest, pelvic, and brain tumors. RESULTS: The maximum tolerated dose of docetaxel was 15 mg/m2 (twice a week) for chest and pelvic cancer patients. The dose-limiting toxicity (DLT) was asthenia and mucosal toxicity (esophagitis or diarrhea in chest and pelvic tumors, respectively). Patients with glioblastomas received 23 mg/m2 (twice a week) without toxicity. Complete response of the chest disease was observed in 3/9 (33%) patients and partial response in 4/9 (44%). Three patients with glioblastoma had a partial response. In pelvic malignancies a high complete response rate was observed (4/9; 45%). Severe monocytopenia and lymphocytopenia were observed during the fourth week of treatment. IgG and IgA immunoglobulins were also reduced. This coincided with the onset of asthenia and severe mucosal toxicity. Asthenia was absent in patients treated for brain tumors, and lymphocyte toxicity was less pronounced. CONCLUSIONS: Docetaxel radiochemotherapy is a promising therapeutic approach for locally advanced cancer. The recommended dose of docetaxel for chest and pelvic cancer patients is 15 mg/m2 twice a week. Patients with brain tumors can be safely treated with higher doses of docetaxel (23 mg/m2 twice a week) without toxicity. The severe immunologic toxicity observed suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) and immunoglobulin administration may be important in the efficacy and tolerance of taxane-based radiochemotherapy. Randomized trials are required to assess whether the efficacy of docetaxel radiochemotherapy depends on the frequency of docetaxel administration during radiation treatment.

Adult↗
PubMed1999

Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial.

PURPOSE: To investigate the activity of docetaxel and granulocyte colony-stimulating factor support (G-CSF) in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with cisplatin. PATIENTS AND METHODS: A total of 60 patients with locoregional and metastatic NSCLC who had relapsed or progressed after first-line treatment with cisplatin-based regimens were enrolled into the trial. Docetaxel at 100 mg/m2 was given as a 1-h infusion with G-CSF (rhG-CSF given s.c. at 150 microg/m2) support from day 2 to day 8 every 3 weeks; all patients received premedication with corticosteroids. RESULTS: In all, 1 (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial response (PR), respectively, for an overall response rate of 25% (95% CI 14.0-35.9%); stable disease (SD) and progressive disease (PD) were documented in 18 (30%) and 27 (45%) patients, respectively. The median duration of response was 20 weeks and the median time to tumor progression was 28 weeks. The median overall survival was 32 weeks and the 1-year survival rate was 23%. A total of 263 courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade 2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4 (7%). Other toxicities were mild. CONCLUSIONS: Docetaxel has considerable single-agent activity in patients with NSCLC who have relapsed or progressed after first-line chemotherapy with cisplatin-based regimens.

Adult↗
PubMed1999

Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: a multicenter phase II trial. Greek Breast Cancer Cooperative Group.

PURPOSE: The activity of the docetaxel-gemcitabine combination in women with disease progression after initial chemotherapy for metastatic breast cancer (MBC) was investigated in a multicenter phase II study. PATIENTS AND METHODS: Fifty-two patients with metastatic breast cancer who had disease relapse or progression after completion of an anthracycline-based front-line regimen were treated with gemcitabine 900 mg/m2 on day 1 and day 8 and docetaxel 100 mg/m2 on day 8. G-CSF 150 mucg/m2/d s.c. was given from day 9 to day 16 and the treatment was repeated every three weeks. The patients' median age was 57 years and the performance status (WHO) was 0 for 26, 1 for 20 and 2 for 6 patients. The treatment was second-line for 27 (52%) and > or = third-line for 25 (48%) patients. All patients were evaluable for response and toxicity. RESULTS: Complete response occurred in seven (14%) patients and partial response in 21 (40%) for an overall response rate of 54% (95% confidence interval (95% CI): 40%-67%). Fifteen (29%) patients had stable disease and nine (17%) progressive disease. Of 25 patients previously treated with taxanes. 11 (44%) responded (1 CR, 10 PR). Interestingly, in four patients with disease progression while receiving docetaxel or paclitaxel monotherapy, the docetaxel + gemcitabine combination achieved partial responses. Responses were observed at all metastatic sites (local disease 62%, lymph nodes 58%, skin 44%, lung 47% and liver 36%) with a median duration of response of 3.6 months (range 1-16) and a median time to disease progression of eight months (range 2-18.5). Grade 3 neutropenia developed in 10 (19%) and grade 4 in five (10%) patients. Neutropenia was associated with infection in four patients without toxic deaths. Grade 3 thrombocytopenia developed in nine (17%) patients and grade 4 in two (4%). Non-hematologic toxicity was usually mild. CONCLUSION: The docetaxel-gemcitabine combination is an active and well tolerated salvage treatment in patients with MBC. Previous treatment with taxanes does not preclude a good clinical response to this regimen.

Adult↗
PubMed1999

Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer.

PURPOSE: To define the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%) had performance status (World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks. RESULTS: A total of 217 chemotherapy cycles were administered. Without recombinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20 mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neutropenia (9% of the cycles) occurred during the whole period of the study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte number was observed; immunophenotyping revealed that all lymphocyte subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%). The median duration of response was 12.5 months, and the median time to tumor progression was 14.5 months. CONCLUSION: The reported combination of docetaxel and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC.

Adult↗
PubMed1999

Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial.

PURPOSE: To evaluate the tolerance and efficacy of the combination of docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one chemotherapy-naive patients with NSCLC were treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel 100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150 microg/m2, subcutaneously) support from day 9 to day 15. Treatment was repeated every 3 weeks. RESULTS: The patients' median age was 64 years. The World Health Organization performance status was 0 to 1 in 39 patients and 2 in 12 patients. Fifteen patients (29%) had stage IIIB disease, and 36 (71%) had stage IV; histology was mainly squamous cell carcinoma (59%). A partial response was achieved in 19 patients (37.5%; 95% confidence interval, 24% to 50%); stable disease and progressive disease were each observed in 16 patients (31.4%). The median duration of response and the time to tumor progression were 5 and 6 months, respectively. The median survival was 13 months, and the actuarial 1-year survival was 50.7%. Grade 4 anemia and thrombocytopenia were rare (2%). Four patients (8%) developed grade 3 or 4 neutropenia, and all were complicated with fever; there was no treatment-related death. Grade 3 or 4 diarrhea occurred in three patients (6%), grade 2 or 3 neurotoxicity in four patients (8%), grade 2 or 3 asthenia in 10 patients (20%), and grade 2 or 3 edema in 10 patients (20%). CONCLUSION: The combination of docetaxel/gemcitabine is well tolerated, can be used for outpatients, and is active for the treatment of advanced NSCLC. This treatment merits further comparison with other cisplatin- or carboplatin-based combinations.

Adult↗
PubMed1998

First-line treatment of advanced nonsmall cell lung carcinoma with docetaxel and vinorelbine.

BACKGROUND: Docetaxel and vinorelbine are active agents in the treatment of nonsmall cell lung carcinoma (NSCLC). The efficacy and toxicity of this combination was evaluated in a Phase II study in patients with advanced NSCLC. METHODS: Forty-six chemotherapy-naive patients (44 men and 2 women with a median age of 64 years) with NSCLC (11 with Stage IIIB and 35 with Stage IV disease) were entered into the study; the World Health Organization (WHO) performance status was 0, 1, and 2 in 32, 11, and 3 patients, respectively. Patients received vinorelbine (25 mg/m2) on Day 1 and docetaxel (100 mg/m2) on Day 2 in cycles repeated every 3 weeks. Granulocyte-colony stimulating factor was given to all patients from Day 3 to Day 10. RESULTS: One hundred and seventy-seven courses of chemotherapy were administered. Adverse events included WHO Grade 4 neutropenia (15 patients), Grade 3/4 thrombocytopenia (3 patients), Grade 3 anemia (2 patients), Grade 2 and 3 neurotoxicity (7 patients and 1 patient, respectively), and Grade 3 fatigue (2 patients). Twenty patients (43%) required hospitalization: 11 (24%) for neutropenic fever (2 deaths from sepsis), and 9 (20%) for nonneutropenic pulmonary infections (2 deaths from cardiopulmonary insufficiency). The median overall survival was 5 months and the 1-year survival was 24%. Four complete responses (9.8%) and 11 partial responses (26.8%) (overall response rate of 36.6%; 95% confidence interval, 21.8-51.3%) were documented in 41 evaluable patients (intent-to-treat: 32.6%). Stable and progressive disease occurred in 13 patients each (31.7%). The median duration of response was 5 months and the median time to progression was 3 months (6 months for the responders). CONCLUSIONS: This schedule of docetaxel and vinorelbine combination is effective but its relatively high incidence of complicated neutropenia precludes its general use in patients with advanced NSCLC.

Adenocarcinoma↗
PubMed1998

Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer.

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.

Adult↗
PubMed1998

Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial.

In this phase I/II study, we investigated the radiosensitising effects of docetaxel in non-small cell lung cancer (NSCLC). 30 patients with stage IIIb (18 patients) and IV (12 patients) NSCLC were treated with 64 Gy of accelerated chest radiotherapy (5-week schedule using a concomitant boost technique) and docetaxel on a weekly basis. The docetaxel starting dose level was 20 mg/m2/week and was escalated by 10 mg/m2 increments in cohorts of 10 patients. Dose-limiting toxicity (grade 3 asthenia) was observed in 6 of 10 patients treated at the 40 mg/m2/week dose level, enforcing a 50% dose reduction in 4 patients. Grade 3 neutropenia was observed in 5 of 30 patients (17%), 3 of which were treated at the high dose level. Peripheral neuropathy occurred in 3 (10%) patients. A significant decrease in the absolute lymphocyte count was observed in all patients; the nadir was reached on day 28 (mean +/- standard deviation (S.D.) = 539 +/- 363/ml) compared with pretreatment values (mean +/- S.D. = 1842 +/- 863/ml; P = 0.002). 6 out of 30 patients (20%) experienced grade 3 oesophagitis, resulting in a 1-2 week delay in overall treatment time. Complete response of the primary tumour was observed in 8 (27%) patients assessed 2 months after treatment. 4 of these patients had disease resistant to previous docetaxel-containing chemotherapy. A partial response occurred in 15 of 30 patients (50%) for an overall response rate of 77% (95% confidence interval (CI) 60-92%). Radiosensitisation with docetaxel is feasible and the recommended dose for further phase II studies is 30 mg/m2/week. Further phase II studies are required to confirm the remarkably high response rate observed in the present trial.

Adult↗
PubMed1998

Neo-angiogenesis in locally advanced squamous cell head and neck cancer correlates with thymidine phosphorylase expression and p53 nuclear oncoprotein accumulation.

Thymidine phosphorylase (Th.P) is an angiogenic factor shown to induce endothelial cell migration and proliferation. On the other hand, loss of wild type p53 function leads to down-regulation of thrombospondin-1, an inhibitor of angiogenesis. In this immunohistochemical study we investigated the intratumoural angiogenesis and thymidine phosphorylase (Th.P) expression in paraffin-embedded bioptical material from 104 locally advanced squamous cell head and neck cancers. The nuclear accumulation of mutant p53 protein and the cytoplasmic expression of bcl-2 protein was also assessed. High vascular grade was observed in 56% and high Th.P tumour cell reactivity in 48% of cases. High microvessel score was associated with an increased percentage of cancer cells expressing thymidine phosphorylase (P = 0.001). Increased p53 nuclear accumulation also correlated with high vascular grade (P = 0.001). High histological grade and absence of bcl-2 overexpression were associated with lymph node involvement (P = 0.002 and P = 0.02 respectively). No correlation of clinically detected lymphadenopathy with angiogenesis and p53 was observed. We conclude that intense neo-angiogenesis in locally advanced squamous cell head neck cancer is a frequent event, which is associated with nuclear p53 accumulation and thymidine phosphorylase overexpression.

Carcinoma, Squamous Cell↗
PubMed1998

First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study.

PURPOSE: To evaluate the efficacy and safety of the docetaxel-cisplatin combination in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naïve patients with histologically confirmed, measurable stage IIIB or IV NSCLC, a World Health Organization (WHO) performance status of 0-2 and adequate bone marrow, renal, hepatic and cardiac function were eligible for the study. Patients received docetaxel (100 mg/m2) as an one-hour infusion on day 1 and cisplatin (80 mg/m2) as a 30-min infusion with appropriate hydration on day 2. Granulocyte colony-stimulating factor (G-CSF; 150 micrograms/m2, SC) was given on days 3 to 13. Treatment was repeated every three weeks. RESULTS: Fifty-three patients were enrolled (28 with stage IIIB and 25 with stage IV). One complete and 23 partial responses were observed (overall response rate (OR): 45%; 95% CI: 34.1%-61.8%). The response rate was 57% and 32% in patients with stages IIIB and IV disease (P = NS). The median time to progression was 36 weeks and the median survival 48 weeks; the one-year survival was 48%. Grade 3-4 neutropenia occurred in 23 patients, 15 of whom were hospitalized for neutropenic fever; two patients died of sepsis. Grade 2 neurotoxicity was observed in six patients and grade 3 in five patients; grade 3 fatigue occurred in seven patients, grade 3-4 mucositis in four patients and grade 3-4 diarrhea in six patients. Mild allergic reactions and oedema were observed in five and four patients, respectively. The median dose intensity was 30 mg/m2/week for docetaxel and 24 mg/m2/week for cisplatin, corresponding to 91% and 89% of the specified protocol doses, respectively. CONCLUSIONS: The docetaxel-cisplatin combination is an active regimen in advanced NSCLC, but hematologic toxicity remains high despite the prophylactic use of G-CSF.

Adult↗
PubMed1998

Salvage treatment with paclitaxel and gemcitabine for patients with non-small-cell lung cancer after cisplatin- or docetaxel-based chemotherapy: a multicenter phase II study.

BACKGROUND: To evaluate the tolerance and efficacy of the combination of paclitaxel and gemcitabine as salvage treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-nine patients with measurable NSCLC (PS 0-1: 80%; stage IV: 84%) who progressed or failed first-line chemotherapy were enrolled. Prior chemotherapy was cisplatin-based with (n = 20) or without (n = 22) docetaxel and docetaxel-vinorelbine (n = 7). Patients received gemcitabine (900 mg/m2 i.v.; days 1 and 8) and paclitaxel (175 mg/m2; day 8) every three weeks: G-CSF (150 micrograms/m2/day s.c.; days 9-15) was given prophylactically to all patients. RESULTS: One (2%) complete and eight (16%) partial responses were achieved (overall response 18%; 95% CI: 4%-24%); 14 patients (29%) had stable disease and 26 (53%) progressive disease. Six responses were observed in 17 patients who responded to first-line chemotherapy. The median duration of response was seven months, the median TTP eight months and the median survival 11 months. The one-year survival rate was 37%. Grade 3-4 neutropenia occured in six (12%) patients, grade 2-3 neurotoxicity in 16 (32%) and grade 2-3 asthenia in 25 (51%). Other toxicities were mild. CONCLUSIONS: The paclitaxel-gemcitabine combination is a well-tolerated and relatively active salvage regimen in patients with NSCLC and it merits further investigation.

Adult↗
PubMed1998

Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref-1) protein: a basis for its role in human disease.

AIMS: Human AP endonuclease 1 (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cleavage of the phosphodiester backbone 5' to the site. HAP1 is also known to be a potent reduction-oxidation (redox) factor, regulating the binding activity of a number of transcription factors. The purpose of the present study was to examine the expression of HAP-1 in a wide range of human tissues. METHODS AND RESULTS: Using a recently developed specific rabbit polyclonal antibody, we performed immunohistochemistry on paraffin-embedded tissue material. Nuclear staining was detected in crypt cells of the small and large intestine, epithelial cells of breast ducts, basal cells of the skin, alveolar cells of the lung, lymphocytes of the marginal zone of the spleen, in the surface epithelium and stromal cells of the ovary and the transitional epithelium of the bladder. Unexpectedly for a presumed nuclear protein, the staining pattern in some cell populations was mainly cytoplasmic (e.g. superficial cells of gastrointestinal tract, Langerhans cells, Leydig cells and spermatocytes, epithelium of the prostate glands), or both cytoplasmic and nuclear (e.g. epithelial cells of thymus, follicular thyroid cells, parietal cells of the stomach, glandular epithelial cells of the cervix, epithelial cells of exocrine pancreas). CONCLUSION: This differential expression in a wide spectrum of cells is indicative of a potential multifunctional action of HAP1, not necessarily restricted to a role in the nucleus.

Antibodies↗
PubMed1998

Oropharyngeal candidiasis as a marker for esophageal candidiasis in patients with cancer.

The present study was designed to determine the frequency of candidal esophagitis in cancer patients with oral thrush. Patients with clinically and microbiologically diagnosed oral candidiasis were evaluated by endoscopy for concurrent esophageal candidiasis. Esophageal involvement was documented by mucosal lesions, microbiological findings of candidal infection in smears of brushing material, positive cultures of brushing material, and histological evidence of mucosal invasion by the yeast. For 21 of the 22 patients studied, there were endoscopic and microbiological findings of candidal esophagitis. Cultures of the brushing material from all 22 patients were positive, while histological evidence was found for 14 patients. Only 10 of the patients had mild esophageal symptoms. It is concluded that oral thrush represents a reliable marker for esophageal candidiasis in patients with cancer. Routine endoscopy is not necessary to confirm the diagnosis; this procedure should be reserved for patients with persistent thrush and symptoms despite antifungal therapy.

Aged↗
PubMed1998

Salvage chemotherapy with paclitaxel, vinorelbine, and cisplatin (PVC) in anthracycline-resistant advanced breast cancer.

The tolerance and the efficacy of the paclitaxel-vinorelbine-cisplatin combination (PVC regimen) was evaluated in 33 patients with anthracycline-resistant stage IV breast cancer, who had disease progression under anthracycline- or mitoxantrone-based chemotherapy. Fourteen (42%) and 19 (58%) patients had primary and secondary resistance to anthracyclines, respectively; 70% had visceral metastases. Patients received vinorelbine (25 mg/m2) followed by paclitaxel (135 mg/m2) in a 3-hour infusion on day 1, and cisplatin (CDDP; 80 mg/m2) on day 2, in a 3-week schedule. A total of 208 chemotherapy courses were administered (median six courses per patient). Grade 3/4 neutropenia occurred in 13 patients (39%), seven of whom were hospitalized for neutropenic fever (5% of the courses). There was no toxic death. Grade 4 thrombocytopenia occurred in two patients (6%) and grade 3 anemia in three patients (9%). Grade 2 and 3 neurosensory toxicity occurred in 11 patients (32%) and two patients (6%), respectively, and grade 3/4 fatigue was observed in four patients (12%). Two (6%) complete and 17 partial responses (52%) (total, 58%; 95% confidence interval, 42%-75%) were documented. Stable disease was observed in eight patients (24%) and progression in six patients (18%). The median duration of response was 6.5+ months. The median survival was 15+ months, and the 1-year survival was 67%. In conclusion, PVC regimen is an active and well-tolerated salvage chemotherapy in patients resistant to anthracycline.

Adult↗
PubMed1998

Treatment of non-small-cell lung cancer with prolonged oral etoposide.

The efficacy and toxicity of chronic administration of oral etoposide was evaluated in 61 patients with inoperable non-small-cell lung cancer (NSCLC). Ten patients received previous chemotherapy, 15 received radiotherapy, and one received both treatments. Twenty-four patients had concurrent cardiac and/or pulmonary impairment, which precluded more intensive treatment. Etoposide was given orally, 100 mg daily for 7 consecutive days and consequently 100 mg every other day for 14 more days in a 28-day schedule. Partial response was observed in 17 patients (28%; 95% confidence interval, 17-39%) and stable disease in 21 (34%). The median duration of response was 6 months (range, 2-34 months). The median survival for responders was 22 months and that of nonresponders was 7 months (p < 0.001). The median survival for all patients was 9 months (range, 1-35 months; 95% confidence interval, 5.69-12.31%). Toxicity was acceptable. Other than alopecia, which was observed in all patients, myelotoxicity was the most common toxicity--particularly leukopenia, which was severe in nine patients. Other less common toxicities included nausea and vomiting, stomatitis, anorexia, and neurotoxicity and were mild. No treatment-related deaths were observed. In conclusion, the regimen was effective and well tolerated with significant survival benefit for the responders. It represents an interesting therapeutic approach, especially in the elderly.

Administration, Oral↗
PubMed1998

Fractionated carboplatin radiosensitization: a phase I dose-escalation study.

Carboplatin is one of the most common drugs used for radiochemotherapy of cancer. However, the best way to combine the drug with fractionated radiotherapy has not been established. In the present study the authors investigated which maximum tolerated daily bolus dose of carboplatin would allow safe radiopotentiation for 10 consecutive radiotherapy days, the scheme being repeated twice during the 6 weeks that a conventional radiotherapy scheme lasts. Seventy-two patients with lung or pelvis malignancies were included in a dose escalation study. Twenty-four patients comprised the first baseline cohort and were treated with radiotherapy alone. The daily dose of carboplatin was escalated starting from 38 mg/m2 daily (for 10 days) and increasing by 7 mg/m2 per day. Six patients were to be included in each cohort. All 12 patients treated at the 38 mg/m2 and 45 mg/m2 dose level completed two cycles of 10-day carboplatin treatment with no grade III-IV toxicity. Granulocyte colony-stimulating factor effectively averted the incidence of neutropenia and allowed the administration of the second carboplatin 10-day cycle in five of six patients at the 52 mg/m2 daily dose level. Platelet grade III-IV toxicity was observed in all 12 patients (six supported with granulocyte colony-stimulating factor and six with granulocyte colony-stimulating factor and recombinant human erythropoietin) treated at the 59 mg/m2 daily dose level and none of them received the second cycle of chemotherapy. Twelve patients were treated at the same dose level using amifostine 500 mg before carboplatin infusion. Two patients interrupted chemotherapy because of severe nausea and vomiting. Nine of 10 who accomplished the 10-day treatment had platelet levels more than 90,000/microl on day 28 and completed the second 10-day cycle without severe toxicity. Acute radiation toxicity did not increase in the carboplatin cohorts. In this study the authors established a high-dose fractionated carboplatin schedule that can be safely administered during radical radiotherapy.

Adult↗