Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting.

BACKGROUND: Casopitant mesylate is a novel, oral neurokinin-1 receptor antagonist with demonstrated antiemetic efficacy. We conducted a randomized, double-blind, controlled phase II trial to evaluate three casopitant doses as part of a triple-therapy regimen for the prevention of nausea and vomiting associated with high-dose cisplatin. The aim of the study was to detect a dose response. PATIENTS AND METHODS: A total of 493 patients with solid tumors receiving a first cycle of cisplatin > or =70 mg/m(2) were randomly assigned among six treatment arms. The primary analysis compared a control arm [ondansetron/dexamethasone (Ond/Dex)] with three investigational treatments (Ond/Dex plus oral casopitant 50, 100, or 150 mg administered daily for 3 days). Two exploratory arms were included: one evaluating a single oral casopitant dose of 150 mg added to standard Ond/Dex and another with 3-day oral aprepitant-based therapy (Ond/Dex plus aprepitant 125 mg day 1, 80 mg days 2-3). RESULTS: The complete response (CR) rate (defined as no vomiting, retching, rescue therapy, or premature discontinuation) was significantly increased in each casopitant arm relative to control over the 120-h evaluation period: 76% (50 mg), 86% (100 mg), 77% (150 mg), and 60% with control (P = 0.0036). The CR rate for the single oral dose regimen was similar to the CR rate reported for the 3-day regimens. No differences were observed in the incidence of nausea or significant nausea among groups in the primary analysis. The most common adverse events related to treatment included headache (n = 10) and hiccups (n = 14). CONCLUSION: All doses of oral casopitant as a 3-day regimen (and likely as a 150-mg single oral dose) in combination with Ond/Dex provided significant improvement in the prevention of cisplatin-induced emesis.

Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and i.v. vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer.

BACKGROUND: The study compared the efficacy of a first-line treatment with day 1 i.v. vinorelbine (NVBiv) and day 8 oral vinorelbine (NVBo) versus docetaxel (DCT) in a cisplatin-based combination in advanced non-small-cell lung cancer, in terms of time to treatment failure (TTF), overall response, progression-free survival (PFS), overall survival (OS), tolerance and quality of life (QoL). METHODS: Patients were randomly assigned to receive cisplatin 80 mg/m2 with NVBiv 30 mg/m2 on day 1 and NVBo 80 mg/m2 on day 8 every 3 weeks, after a first cycle of NVBiv 25 mg/m2 on day 1 and NVBo 60 mg/m2 on day 8 (arm A) or cisplatin 75 mg/m2 and DCT 75 mg/m2 on day 1 every 3 weeks (arm B), for a maximum of six cycles in both arms. RESULTS: From 2 February 2004 to 1 January 2006, 390 patients were entered in a randomised study and 381 were treated. The patient characteristics are as follows (arms A/B): metastatic (%) 80.5/84.8; patients with three or more organs involved (%) 45.3/40.8; median age 59.4/62.1 years; male 139/146; squamous (%) 34.2/33.5; adenocarcinoma (%) 41.6/39.3; median TTF (arms A/B in months) [95% confidence interval (CI)]: 3.2 (3.0-4.2), 4.1 (3.4-4.5) (P = 0.19); overall response (arms A/B) (95% CI): 27.4% (21.2% to 34.2%), 27.2% (21.0% to 34.2%); median PFS (arms A/B in months) (95% CI): 4.9 (4.4-5.9), 5.1 (4.3-6.1) (P = 0.99) and median OS (arms A/B in months) (95% CI): 9.9 (8.4-11.6), 9.8 (8.8-11.5) (P = 0.58). The median survival for squamous histology was 8.87/9.82 months and for adenocarcinoma 11.73/11.60 months for arms A and B, respectively. Main haematological toxicity was grade 3-4 neutropenia: 24.4% (arm A) and 28.8% (arm B). QoL as measured by the Lung Cancer Symptom Scale was similar in both arms. CONCLUSIONS: Both arms provided similar efficacy in terms of response, time-related parameters and QoL, with an acceptable tolerance profile. In the current Global Lung Oncology Branch trial 3, NVBo was shown to be effective as a substitute for the i.v. formulation. This can relieve the burden of the i.v. injection on day 8 and can optimise the hospital's resources and improve patient convenience.

A phase II study of intravenous navelbine and doxorubicin combination in previously untreated advanced breast carcinoma.

PURPOSE: The combination of vinorelbine and doxorubicin, two very active drugs in metastatic breast cancer, has demonstrated impressive results in terms of efficacy, at the price of cardiac toxicity (10% grades 2-4) due to the cumulative dose of doxorubicin delivered. This study was designed to divide the dose of doxorubicin into two administrations (day 1 and 8) in order to reduce the toxicity profile, while keeping the same level of efficacy. PATIENTS AND METHODS: Thirty-eight chemotherapy-naïve metastatic breast cancer patients entered into the study and were treated with vinorelbine, 25 mg/m(2), and doxorubicin, 25 mg/m(2), both on days 1 and 8, every 3 weeks. Thirty-seven patients were evaluable for efficacy and 38 for tolerance; 71% of the patients presented with visceral metastases. RESULTS: Patients received a median of seven cycles and 94.9% of the intended dose intensity of both drugs. Grade 3-4 neutropenia was reported in 10% of cycles. Alopecia was reported in 89.5% of the patients, and grade 2 nausea/vomiting in 9.3% of the cycles. Grade 1-2 cardiac toxicity was noted in 23.7% of the patients. The objective response rate of the patients was 78.4% (nearly 81% for patients with visceral metastases); the median duration of response was 11.6 months, the median survival 21.6 months, and the 1-year survival 75.2%. CONCLUSION: This schedule of vinorelbine/doxorubicin represents an active and well-tolerated combination.

[Evaluation of efficacy and toxicity of docetaxel (Taxotere) in patients with advanced mammary gland cancer]. / Ocena skutecznosci i toksycznosci docetakselu (Taxotere) u chorych na zaawansowanego raka gruczolu piersiowego.

Twenty women with advanced breast cancer were treated with Docetaxel. In 50% of cases partial remission with median duration of 7.1 months was obtained. The median survival time was 18 months. Stabilization of disease with median duration of 5.5 months was obtained in 45%. The median survival in this group of patients was 15.3 months. The pervious antracycline-based chemotherapy did not influenced the results. The most common side effect was neutropenia (G3 in 80% of pts) and alopecia, but the chemotherapy tolerance was satisfactory.

[Evaluation of efficacy and toxicity of tamoxifen in patients with advanced chemotherapy resistant ovarian cancer]. / Ocena skutecznosci i toksycznosci tamoksyfenu u chorych na zaawansowanego, opornego na chemioterapie raka jajnika.

47 patients with advanced ovarian cancer after routine treatment were treated with tamoxifen. Objective response rate (CR + PR) was 6.4%. 46.8% patients had stable disease with median time of stabilisation 6.9 m. Because of low toxicity and non satisfactory results of second line chemotherapy tamoxifen seems to be a useful treatment for this group of patients.

[Evaluation of efficacy and toxicity of PC chemotherapy (cisplatin, cyclophosphamide) administered with amifostine in patients with clinically advanced ovarian cancer]. / Ocena skutecznosci i toksycznosci chemioterapii PC (cisplatyna i cyklofosfamid) podanej pod oslona amifostyny u chorych w róznym stopniu zaawansowania klinicznego raka jajnika.

Twenty patients with advanced ovarian cancer were treated with chemotherapy PC (cisplatin 100 mg/m2, cyclophosphamide 1000 mg/m2) administered with amifostine. Sixty five percent of patients had objective response with 25% complete response rate. Tolerance of treatment was satisfactory. Only in 1 patients side effects were the reason of treatment interruption. Amifostine markedly decreases chemotherapy toxicity, mainly hematological and does not seem to influence the efficacy of chemotherapy.

[Evaluation of selected clinical prognostic factors in patients with non-granulomatous lymphomas]. / Ocena wybranych klinicznych czynników rokowniczych u chorych na chloniaki nieziarnicze.

Several selected clinical prognostic factors were analyzed in the group of 253 patients suffering from lymphoma. Albumin serum level, performance status, Ann Arbor stage were found to be the important factors according to multivariative analysis by Cox in the group of patients with low grade lymphomas. Performance status and LDH serum level were such factors in the high grade group. More intensive chemotherapeutic regiments should be employed in the group of patients presenting those risk factors.

[Results of tamoxifen treatment in patients with advanced breast cancer]. / Wynik leczenia tamoksyfenem chorych na zaawansowanego raka sutka.

The results of advanced breast cancer therapy with tamoxifen have been evaluated. The objective response to the drug has been achieved in 32 (31.7%) patients, and a 2-year survival in 52% of cases. A correlation between the localization of lesions and response rate has been found. The best results have been achieved in localized lesions and lymph nodes metastases. Low toxicity of the drug enables achievement of results comparable to those seen in all types of the hormonal therapy, except androgens.

[Late hematologic status after chemotherapy observed in patients 3 to 10 years after treatment]. / Pózne powiklania hematologiczne po leczeniu chemicznym obserwowane u pacjentów w 3 do 10 lat po leczeniu.

The aim of the present study is the evaluation of late hematological complication in patients who received aggressive chemotherapy, and were observed 3, 5 and 10 years after treatment was completed. In the group of 35 patients, besides high percent of early hematological complications, there was only one case of anemia grade 2 (acc. to WHO score). We concluded that the hematological recovery after aggressive chemotherapy was satisfactory. No secondary hematological malignancies have been found.

[Comparison of effectiveness of adriamycin and epirubicin administered in the CHOP protocol to patients with malignant non-hodgkin's lymphoma]. / Porównanie skutecznosci adriamycyny i epirubicyny stosowanych w schemacie CHOP u chorych na nieziarnicze chloniaki zlosliwe.

In a group of 30 patients with the diagnosis of malignant non-Hodgkin lymphoma of high histological malignancy, a prospective randomized study was carried out concerning the effectiveness and toxicity of the CHOP chemotherapy using adriamycin vs epirubicin. The effectiveness and tolerance of both treatment programmes are comparable. Good tolerance of the used epirubicin dose encourages to its increase in combined chemotherapy programmes in order to achieve higher therapeutic effectiveness.

[A rare case of dissemination of anaplastic oligodendroma outside the central nervous system]. / Rzadki przypadek rozsiewu anaplastycznego skapodrzewiaka poza osrodkowy uklad nerwowy.

A rare case is reported of primary brain tumour with histological features of anaplastic oligodendroglioma, with metastases outside the central nervous system. Of interest is a short remission after treatment with cyclophosphamide and vepesid which shows that this type of tumour is sensitive in a way to chemotherapy.

Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer.

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

[Results of delayed treatment of patients with malignant tumors of the lymphatic system]. / Przyczyny opóznienia leczenia chorych na zlosliwe nowotwory ukladu limfatycznego.

The causes, with considerably influence the advancement of cancer process have been investigated in patients with lymphatic system tumours admitted to the Department of Chemotherapy at the Center of Oncology in Cracow. It has been revealed, that the delay in the treatment was mainly due to false first diagnosis as well as the negligence of the symptoms by the patients themselves and also to consulting medically unrecognized "healers" before undertaking proper, specialized treatment. It has been observed, that more than every fourth patient took advice of "non-doctors", i.e. bioenergy-therapists, incompetent healers, herbalists and so forth. These factors by influencing further delay in the treatment, diminish its chances.