Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial.

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.

SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results.

BACKGROUND: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. RESULTS: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). CONCLUSION: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times.

Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy.

Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.

Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group.

PURPOSE: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE. RESULTS: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P =.127 and P =.023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P =.023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P =.017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting. CONCLUSION: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.

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.

A multicenter, double-blind comparison of i.v. and oral administration of ondansetron plus dexamethasone for acute cisplatin-induced emesis. Ondansetron Acute Emesis Study Group.

A total of 530 patients were treated in this multicenter, double-blind, double-dummy, parallel group study to compare the anti-emetic efficacy and safety of a once daily ondansetron oral regimen with a once daily i.v. dosing regimen over a 24 h period, administered to patients prior to receiving cisplatin (50 mg/m2 or greater) chemotherapy. Patients were randomized to receive a single dose of ondansetron plus dexamethasone given either orally (ondansetron 24 mg and dexamethasone 12 mg, n=262) or i.v. (ondansetron 8 mg and dexamethasone 20 mg, n=268). Complete control of emesis (i.e. no emetic episodes, no rescue and no premature withdrawal) was achieved for 85% of patients (224 of 262) in the oral group and 83% (223 of 268) in the i.v. group. No nausea was reported in 70% of patients in the oral group and 68% in the i.v. group. There were no statistically significant differences between the two groups for any of the assessments of efficacy, which included time to first emetic episode, number of emetic episodes and the worst grade of nausea occurring over the 24 h study period. Once daily ondansetron oral and i.v., in combination with dexamethasone, was well tolerated in this study. In conclusion, once daily oral ondansetron 24 mg plus dexamethasone is equally effective in the control of emesis and nausea induced by highly emetogenic chemotherapy as once daily ondansetron 8 mg i.v. plus dexamethasone.

Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study.

The efficacy and toxicity profile of gemcitabine was evaluated in this phase II study of chemonaive patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). Eighty patients (62 males, 18 females) were entered into this study. The disease stage was IIIA in ten patients, IIIB in 32, and IV in 38 patients. The median age was 61 (range 41 - 78). Karnofsky performance status was > or = 80 in 88% of patients. All patients were chemonaive, but five patients had received prior radiotherapy and 34 patients had undergone prior surgery. Gemcitabine 1250 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, and 15 of a 28-day cycle. Patients received up to nine cycles (median three cycles). Of 872 doses 815 (93%) were administered without dose delay or modification. Of the 80 patients enrolled, 76 were evaluable for efficacy analysis, and 16 patients had a partial response for an overall response rate of 21.1% (95% CI, 11.9-30.3%). A further 47 patients (61.8%) had stable disease. Partial responses were seen in eight of 41 stage III patients (19.5%) and in eight of 35 stage IV patients (22.9%). The median time to progressive disease was 4.6 months. Median survival for all 80 patients was 7.1 months. Haematological toxicity was mild with grade 3 4 neutropenia in 6.3% of patients, grade 3 thrombocytopenia in 3.8% of patients, and grade 3 anaemia in 2.5% of patients. Grade 3 non-laboratory toxicity was: somnolence (1.3% of patients), infection (1.3%), nausea and vomiting (6.4%) and dyspnoea (5.1%). This study confirms that single-agent gemcitabine is active in advanced NSCLC and its well-tolerated safety profile makes it particularly suited to outpatient use.

Multimodality treatment of noninflammatory stage IIIb breast cancer.

BACKGROUND AND OBJECTIVES: The 1990s have established the contribution of multimodality therapy in the management of IIIb noninflammatory breast cancer (IIIb NIBC), by reducing the odds of recurrence and death. METHODS: A total of 300 women with IIIb NIBC received a multimodality therapy. The treatment consisted of neoadjuvant chemotherapy [FAC (5-fluorouracil, Adriamycin, cyclophosphamide) regimen], radical (Halsted) mastectomy or modified (Patey mastectomy), postoperative radiotherapy, and adjuvant chemohormone therapy [FAC regimen + cyclophosphamide, 5-fluorouracil and methotrexate (CMF) regimen or Tamoxifen]. RESULTS: Complete or partial clinical response (CR or PR) after neoadjuvant chemotherapy was obtained in 83% patients. Ninety-nine patients (33%) survived 5 years without evidence of disease (NED). The uni- and multivariate analyses factors that had significant influence on the treatment results were: clinical response to neoadjuvant chemotherapy, pathological tumor size, and microscopical status of the axillary lymph nodes. CONCLUSIONS: We conclude that neoadjuvant FAC regimen chemotherapy is very effective in producing objective tumor regression and offers the benefit of radical mastectomy to patients with previously unresectable IIIb NIBC.

Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study.

The study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.

A multicenter study of recombinant human erythropoietin (epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy.

Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p < 0.0001) improvement in mean WHO performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

[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.

[Further studies on the efficacy of inductive chemotherapy in patients with locally advanced stage of mammary cancer]. / Dalsze badania nad skutecznoscia indukcyjnej chemioterapii u chorych na miejscowo zaawansowanego raka sutka.

In a period from 1.01.1979 to 31.12.1984 in the Oncology Centre, Department in Cracow, 202 female patients with locally advanced stage of mammary cancer (T3-4 a-d, N 2-3) were treated with inductive chemotherapy with following local treatment completed with maintenance treatment. The aim of this study is to try to show distant results of the treatment based on current experiences and to analyse failure reasons. Kaplan-Mayer method was used to estimate probability of 3 and 5 year lasting surviving.

[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.

[Use of ifosfamide in multidrug therapy of small cell lung carcinoma]. / Zastosowanie ifosfamidu w wielolekowej chemioterapii drobnokomórkowego raka pluca.

Own concept of small cell lung carcinoma (SCLC) chemotherapy with multidrug regimen including ifosfamide, adriamycin, and etoposide is presented. In the pilot trial, 67% of remissions in patients with localized, and 33% in patients with disseminated neoplastic process were achieved. Proposed therapy has moderate toxicity, markedly lower than that of the regimen including cis-platin. No nephrotoxicity is worth emphasizing. The authors suggest that proposed regimen may be of value in patients in whom combined chemo- and radiotherapy is foreseen.