A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results.

BACKGROUND: The equivalent efficacy between SB3, a proposed trastuzumab biosimilar, and the trastuzumab reference product (TRZ) in terms of the breast pathologic complete response rate after neoadjuvant therapy in patients with early or locally advanced human epidermal growth factor receptor 2-positive breast cancer was demonstrated in the previous report. Here, we report the final safety, immunogenicity and survival results after neoadjuvant-adjuvant treatment. PATIENTS AND METHODS: Patients were randomised 1:1 to receive neoadjuvant SB3 or TRZ for 8 cycles concurrently with chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide). Patients then underwent surgery, followed by 10 cycles of adjuvant SB3 or TRZ as randomised. End-points included safety, immunogenicity, event-free survival (EFS) and overall survival through the adjuvant period. RESULTS: Of 875 patients randomised, 764 (SB3, n = 380; TRZ, n = 384) completed the study. The median follow-up duration was 437 days in the SB3 group and 438 days in the TRZ group. The incidence of treatment-emergent adverse events was comparable between groups (SB3, 97.5%; TRZ, 96.1%) during the overall study period. Up to the end of study, the overall incidence of antidrug antibody was low in both treatment groups (3 patients each). EFS was comparable between groups with a hazard ratio (SB3/TRZ) of 0.94 (95% confidence interval, 0.59-1.51) and EFS rates at 12 months of 93.7% for SB3 and 93.4% for TRZ. CONCLUSIONS: Final safety, immunogenicity and survival results of this study further support the biosimilarity established between SB3 and TRZ. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149524); EudraCT (2013-004172-35).

[Combined therapy and radiotherapy in stage-II Hodgkin disease].

The aim of the study was to raise efficacy of combined treatment of stage II Hodgkin's disease by optimization of fractionation and volume of irradiation. It included 179 patients with involvement of supradiaphragmatic lymph nodes treated in 1986-2006. It was found that multi-fractionation was followed by lower frequency of relapse as compared with standard regimens as well as rates of early ones. The most efficient dosage was 30-36 Gy as far as frequency, term of relapse occurrence and recurrence-free survival were concerned.

[Comparative evaluation of clinical efficacy of combined treatment (surgery and radiotherapy) for extremity soft-tissue sarcomas in patients who underwent organ-saving operations].

Clinical efficacy of combined treatment of 383 patients who had undergone conservative surgery for extremity soft-tissue sarcomas (combined treatment -188; surgery alone - 195, control) was assessed. The comparison, which included prognostic factors, established the advantages of combined treatment in all groups. Thus, overall 5-year survival time was in 64.3+/-2.8%, with combined treatment - 72.2+/-3.3% and surgery - 56.8+/-3.5%, t>2. Application of radiotherapy as a component of combined modality treatment made feasible a wider range of organ-saving operations. Differences in the frequency of postoperative complications after surgery and combined treatment were insignificant and of similar patterns.

[Comparative clinical assessment of the factors determining the volume of operations for sarcomas of the extremity soft tissues].

In an analysis of data of 526 patients with carcomas of the extremity soft tissues the factors influencing the decision on the volume of surgery were determine. The 5 year survival of patients subjected to amputations was considerably lower than after sparing operations. Amputations were mostly made for local recurrences of the disease, neoplasm larger than 15 cm in diameter, low-differentiated sarcomas, with infiltration of the tumor into the bone and/or periosteum and localization of the tumor in distal parts of extremities. The rates of 5 year survival among the patients with malignant tumors of the extremity soft tissues subjected to sparing operations were found to be higher after combined program of treatment (operation + radiation therapy).

[Interscapular-thoracic amputation]. / Mezhlopatochno-grudnaia amputatsiia.

An analysis of results of treatment and prostheses of 89 patients with malignant tumors of the upper extremities and shoulder girdle has shown that among the tumors there were osteogenous sarcomas, chondroid sarcomas, nonclassified sarcomas, reticulosarcomas, angiosarcoma, fibrohistocytic sarcoma, Euring's sarcoma, solitary myeloma, giant cells tumors. Interscapular-thoracic amputations were performed in all the patients. The overall survival rate was (28.6 +/- 8.3)%. An orthosis and a modified prosthesis developed at the research institute of prostheses named after prof. G. Albrekht are recommended for rehabilitation of invalids.

[Randomized trial of two administration schedule of bonephos (Clodronate) in patients with painful bone metastasis]. / Randomizirovannoe issledovanie dvukh skhem vvedeniia bonefosa (Klodronata) u bol'nykh s metastazami v kosti soprovozhdaiushchimisia bol'iu.

A randomized study of two intravenous schedules of Clodronate showed that a single 4-hour infusion of 1500 mg Clodronate proved significantly more effective than the traditional 2 hours infusion of 300 mg during 5 days. The regimen may prove preferable in therapy of patients with painful bone metastases.

[Treatment of lung metastasis in patients with soft-tissue sarcoma]. / Lechenie legochnykh metastazov u bol'nykh sarkomami miagkikh tkanei.

The study group included 104 patients with soft-tissue sarcoma and metastases into the lung, treated at the Institute Clinic in 1960-1992. Surgery for lung metastasis was given to 10 and chemotherapy-to 48 patients; the remaining 48 cases received treatment for symptoms only. Overall 5-year survival was 13.5% (after surgery-30.0%; chemotherapy-19.1%). All the 46 patients treated for symptoms died within two years after detection of lung metastasis. Chemotherapy proved effective in the treatment of multiple metastasis when detected shortly after removal of the first lesion.

[Use of adriamycin in the treatment of metastatic breast cancer]. / Lechenie metastaticheskikh form raka molochnoi zhelezy s ispol'zovaniem adriamitsina.

Adriamycin (alone and as a component of FAC scheme) should be administered to patients with disseminated breast cancer resistant to cytostatic drugs. This treatment is followed by remission and arrests the process for an average of 9 months (in some cases up to 30 months). Mean doses of 30-40 mg should be given to outpatients on days 1 and 8 of each course, with intervals between courses being 21-28 days. No apparent side-effects are observed. The total dose should be as high as 450-550 mg. Adjuvant antiestrogen treatment (tamoxifen) should be given to pre- and menopausal patients.

[Comparative evaluation of the results of mono- and polychemotherapy of disseminated forms of breast cancer using the CMFVP program and anthracycline antibiotics (carminomycin and adriamycin)]. / Sravnitel'naia otsenka rezul'tatov mono- i polikhimioterapii disseminirovannykh form raka molochnoi zhelezy s ispol'zovaniem programmy SMFVP i antratsiklinovykh antibiotikov (karminomitsina, adriamitsina).

A total of 203 out patients with disseminated cancer of the mammary glands subjected to chemotherapy were followed up. Of these, 44 patients were treated according to the CMFVP program, 66 were subjected to monochemotherapy with carminomycin, 42 were treated with combinations of carminomycin and dibromdulcytol, 14 patients received monochemotherapy with adriamycin and 37 polychemotherapy according to the scheme of fluorouracil + adriamycin + cyclophosphamide. In addition to the early-demonstrated efficacy of adriamycin and the Cooper scheme, the comparative estimation of the treatment programs showed that carminomycin, a new antitumor antibiotic made in the USSR, had an obvious activity when used alone or in combination with dibromdulcytol, an alkylating agent, in the treatment of primary extended forms, relapses and metastases of mammary tumors. The data indicate that wide use of carminomycin which is comparatively low toxic is advisable in the treatment of disseminated cancer of the mammary gland.

[Results of a clinical study of carminomycin in primary disseminated forms, recurrences and metastases of breast cancer]. / Rezul'taty klinicheskogo izucheniia karminomitsina pri pervichno-rasprostranennykh formakh, retsidivakh i metastazakh raka molochnoi zhelezy.

A more than 50% regression of tumor was observed in 19% of 64 patients treated with carminomycin for advanced primary breast cancer, its recurrences and metastases. A clinically-significant effect of treatment was recorded in 42%, while tumor process was arrested for at least 3-4 months in 37% of cases. The index of more than 50% regression of tumor rose to 28% in a group of 27 patients, following repeated courses of the drug. Only a slight toxic side--effect was observed, repeated courses included. Moderate leukopenia and a slight cardiotoxic effect were registered in 17%; phlebitis--in 12%. Carminomycin treatment should be recommended for advanced primary breast cancer, its recurrences an metastases, when other chemotherapeutic means fail to stop tumor process.

[Characteristics of the formation, course and outcome of lymphogranulomatous caverns in the lungs]. / Nekotorye osobennosti formirovaniia, techeniia i iskhoda limfogranulematoznykh kavern v legkikh.

Clinico-roentgenological manifestations of specific destructive lesions in the lung in cases of Hodgkin's disease are described. The authors' findings suggest that disintegration focus formation is determined by duration of diseases, rapid regression of specific lesion of the lung as a result of therapy and suppression of reparative regeneration of lung tissue by corticosteroids and possibly, cytostatic drugs. However, a course of cytostatic therapy eventually resulted in the regression of lung tissue alterations and dissolution of disintegration cavities in most cases.