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.

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.

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.

The results of Vepesid therapy in the treatment of malignant lymphomas.

Twenty-three patients with Hodgkin's disease and non-Hodgkin's lymphomas were treated by Vepesid. The dose of the drug was 150 mg/m2 daily for 5 consecutive days. This schedule was repeated every 3 weeks. The percentage and response were estimated according to WHO scale. There were complete responses and 6 partial responses lasting 13.7 and 5 months, respectively, on the average. The results of Vepesid therapy depended on the efficiency of previous treatment.

An attempt at applying epiadriamycin to the patients for whom doxorubicin is cardiologically contraindicated.

Administrating Epi-ADR (Epiadriamycin) to the patients for whom ADR was cardiologically contraindicated did not cause significant complications. No complications occurred in the patients treated with Epiadriamycin, after they had completed a full course of maximal dose of ADR. The trial was conducted in close cooperation with a cardiological intensive care unit which is an essential arrangement in such clinical situation, until the optimal therapeutical method of administrating Epi-ADR is defined with special attention devoted to its critical dose.

An attempt at topical DNCB immunomodulation in advanced malignant melanoma.

Nineteen patients with malignant melanoma metastatic to the skin, subcutaneous tissue or lymph nodes were treated with DNCB applied to the lesion. None of the patients was amenable to any other form of treatment. During the 20-month follow-up, complete remission occurred in 3 patients and partial remission in 3 patients, 1 patient showed stabilization of the disease, and in the remaining 12 not even transient improvement was observed.

Results of combined treatment of patients with locally advanced breast cancer.

Eighty-seven women with previously untreated locally advanced, inoperable breast cancer were treated by induction chemotherapy combined with subsequent local and systemic treatment. Inflammatory breast cancer was diagnosed in 72 (87.7%) of these patients. In the remaining 15 patients, cancer of the breast in stage T3-4 N2b-3 according to the UICC classification was diagnosed. After remission induction, the patients were irradiated or operated upon. Maintenance chemotherapy was given after local treatment. The 3-year survival rate (61.5%) in the group of patients treated by surgery was significantly higher than the patients treated by irradiation (32.4%) or chemotherapy alone (12.5%). On this basis, a new program of treatment of locally advanced, inoperable breast cancer has been proposed.

Prognostic factors in advanced metastatic and recurrent melanoma treated with DTIC.

Thirty-five patients with recurrent and 25 patients with metastatic malignant melanoma after previous radical locoregional surgery were treated with DTIC at the Institute of Oncology in Kraków between 1976 and 1981. Complete and partial remissions were observed in 19/60, i.e., in 31% of the patients. Our results show an advantage for patients with locoregional recurrence, soft-tissue and lung metastases, provided that the largest deposit is no larger than 5 cm in diameter. There is little chance of remission in patients with liver and bone metastases.

[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.

[Role of carboplatin in treating patients with advanced ovarian cancer]. / Rola carboplatyny w leczeniu chorych na zaawansowanego raka jajnika.

Results of Carboplatin treatment of ovarian cancer were presented. Drug resistance was observed during therapy of first course type. Objective response to treatment was observed with 5 patients from 27 ones (19%).

[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.

[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.

[Studies of the clinical use of cycloplatin--a new derivative of cisplatin]. / Badania nad zastosowaniem klinicznym cycloplatyny--nowej pochodnej cisplatyny.

The preliminary results of Cycloplatin in non small cell lung cancer were presented. Cycloplatin is a new derivative of Cisplatin but less nephrotoxic. Its. referring preparation is Carboplatin 14% remissions were found in the cases of inoperable non small cell lung cancer and 12% remissions in advanced ovarian cancer. 84% of patients suffered from vomiting what was the most common reported side-effect.

[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.

[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.

[Results of adjuvant therapy with the preparation Poly-a Poly-u in patients with malignant melanoma during a 10-year observation]. / Wyniki adjuwantnej terapii preparatem Poly-A Poly-U u chorych na czerniaka zlosliwego w 10-letniej obserwacji.

During 10 years patients with malignant melanoma were followed up after radical removal of primary tumour and metastatic regional lymph nodes, the half of whom was given immunomodulation with the preparation Poly-A Poly-U in a controlled clinical trial. It was found that the performed immunomodulation exerted slight effect on the course of malignant melanoma causing later development of recurrence, less dynamic course of the disease, longer asymptomatic periods in relation to the control group. No effect of the drug administration was observed on longterm survival.

[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.

[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.

[Assessment of causes for delayed treatment in patients with malignant neoplasms ]. / Ocena przyczyn opóznionego leczenia chorych na nowotwory zlosliwe.

Investigation of the causes of delay in the treatment of patients with malignant neoplasms indicates that medium time of delay caused by patient has been 7 months, and caused by physician 9 months. Investigations indicate also that time of waiting for admission to the Oncology Center has been averaging 3 weeks. It has been found that every 9-th patient has been under non medical care for average period of 7 months.

[Results of chemotherapy of cancer of the stomach]. / Wyniki chemioterapii raka zoladka.

45 patients with advanced gastric cancer received palliation chemotherapy in the period from October 1975 until December 1985. Remission have been obtained in 9 patients including complete remission in 3 (6.6%) and partial in 6 (8.1%). Mean survival for the whole group has been 11.6 months, in patient with remission 16.4 months and in patients not responding to treatment 5.6 months.