Biological and clinical features of non-Hodgkin's lymphoma in the elderly.

PURPOSE: The incidence of non-Hodgkin's lymphomas (NHLs) in elderly people has increased in recent years because the world population is getting older. The aim of this study was to compare the biological and clinical features in patients diagnosed with NHLs younger and older than 65 years, and the possible influence of age on the choice of optimal therapeutic approach. METHODS: We retrospectively evaluated 193 patients with NHLs: 111 (68%) were <65 years and 82 (42%) ≥65 years. The following parameters were analysed: age, gender, clinical stage, International Prognostic Index (IPI), histological type, presence of B symptoms, disease localization, presence of bulky mass, Karnofsky performance status (PS), comorbidities, blood counts, liver and renal function and serum LDH. RESULTS: Elderly patients had statistically more frequent indolent NHLs (p=0.036), IPI 3 and 4 (p<0.0001), presence of comorbidities (p<0.001), and less frequent presence of bulky disease (p7equals;0.043). Response to therapy was different in the 2 age groups: 29% of patients ≥65 years achieved complete remission (CR) in contrast to 71% of patients <65 years (p<0.001). The most frequent cause of death was disease progression (PD) (86% of younger patients and 71% of elderly patients (p7equals;0.150). Older patients died more frequently because of comorbidities compared younger ones (21 and 107percnt;, respectively; p=0.250), and had more complications of therapy (8.1 and 47percnt;, respectively (p=0.320). Overall survival (OS) was shorter in older patients in all lymphoma types: indolent lymphoma (36 vs. 17 months), aggressive (22 vs. 20 months) and very aggressive (14 vs. 1 months). Multivariate analysis showed that parameters for shorter survival in the elderly were Karnofsky PS <60, increased serum LDH and treatment toxicity. CONCLUSION: In elderly NHLs patients, treatment response and survival are significantly poorer. Since older patients mostly died of PD, they should be treated with standard regimens and best supportive measures.

Disconnection of chamber and catheter as a complication of central venous catheter type port-a-cath.

The use of a central vein catheter (CVC) type port-a-cath (VPS), apart from the comfort it provides to the patient undergoing chemotherapy, also carries certain complications. In this study, our patient was subjected to chemotherapy after a radical breast cancer operation and was given a CVC type VPS. After further care, a rare complication was verified--disconnection of the chamber and catheter, which one was visually identified in the right heart chamber. As the patient was vitally endangered, she was immediately hospitalized and the catheter was removed by catheterization of the right femoral vein, with scopic imaging. Early diagnosis and localization of the problem prevented more severe complications and mortality.

Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study.

The aim of this randomized four-arm phase III study was to evaluate whether there is a difference in activity between regimens containing dacarbazine and regimens without dacarbazine in metastatic melanoma, whether there is a dose-effect relationship for dacarbazine, and whether non-dacarbazine-containing aggressive regimens are in any way superior to non-aggressive ones. A total of 219 patients with metastatic cutaneous melanoma were included in this study; 196 of them were evaluable for activity. The patients were randomized into four treatment arms: arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600 mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine), vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin 30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days 1-10. The four arms were well balanced with regard to patient- and disease-related characteristics. On an intend-to-treat basis, the response rate was 11 out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in arm C and nine out of 60 (15%) in arm D. There was a large overlap between the 95% confidence intervals and no significant differences in the response rates between the four arms. Median survival in the four treatment arms was 4, 5, 6 and 4 months, respectively, again with no significant differences. Median survival for responders (8, 11, 10 and 13 months, respectively) in all four arms was significantly longer than in non-responders (4, 3, 5 and 4 months, respectively). Arms A, B and C were significantly more toxic compared with arm D, which was for all practical purposes devoid of toxicities. The efficacy of all four regimens thus appeared comparable both in terms of response rate and survival. Responders in all four arms achieved a survival benefit. There does not seem to be a dose-effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm D, might be well suited for 'fragile' or elderly patients due to the lack of toxicity.

Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.

This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving cisplatin 120 mg/m(2), mitomycin C 8 mg/m(2) and vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving carboplatin 500 mg/m(2) with the same doses of mitomycin C and vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and tumor histological grade (I+II vs. III). In the cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the carboplatin arm. The advantage for patients receiving carboplatin instead of cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the carboplatin than in the cisplatin arm (P=0.012). Thus, substitution of cisplatin by carboplatin in the combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.

A two-step reevaluation of high-dose amsacrine for advanced carcinoma of the upper aerodigestive tract: a pilot phase II study.

Results of amsacrine studies in different solid tumors with a dose of 85 mg/m2/24 h x 1 quo 3 weeks have been, in general, disappointing. Although only a few patients with head and neck cancer have been included in broad phase II studies, several responses have been reported, but detailed data concerning responders are lacking. In the present study, amsacrine (Amsidil, Godecke-Parke Davis) was administered at an increased dose of 85 mg/m2/24 h x 3 (total dose per cycle 255 mg/m2) quo 3-4 weeks. 25 patients with advanced carcinoma of meso and hypopharynx were included in the first step of this phase II study (11/25 with histological grades I/II and 14/25 with histological grades III/IV; 10/25 pretreated with radical radiotherapy and 15/25 previously untreated), and 5 patients with undifferentiated carcinoma of the nasopharyngeal type (UCNT), all previously treated. 5/30 patients achieved a complete response (CR) and 5/30 a partial response (PR), the overall response rate being 10/30. Regarding the histology grade, only 1/11 patients with grade I/II carcinoma of meso and hypopharynx achieved a PR with no CR, but 5/14 with grade III/IV from the same group achieved a CR. Out of 10 pretreated patients only one achieved any response and none of the 5 patients with UCNT. Thus, in the second step of this study, high dose amsacrine was evaluated in the target group of previously untreated patients with advanced grade III/IV carcinoma of meso and hypopharynx. 20 patients were included in the second step and all were evaluable for activity. A CR was achieved for 6/20 patients and a PR for 7/20 patients (response rate 65%, 95% confidence interval 44%-86%). Hematological toxicity from both steps included grade IV granulocytopenia in 25/50 patients (50%, 95% confidence interval 36%-64%) and grade IV thrombocytopenia in 18/50 patients (36%, 95% confidence interval 23%-49%). High dose amsacrine seems to be a toxic, but very effective drug as first-line treatment for poorly differentiated carcinoma of meso and hypopharynx, and further studies seem warranted.

Randomized study of zorubicin versus zorubicin-cisplatin in undifferentiated carcinoma of the nasopharynx (UCNT)

BACKGROUND: The most active chemotherapy regimens in UCNT were those combining anthracyclines (doxorubicin or epirubicin) and cisplatin. Our previous pilot study on 37 patients treated with the zorubicin-cisplatin combination with a RR of 67% and literature data about other anthracyclines such as epirubicin achieving a response rate of over 50% were the basis of this randomized study comparing efficacy and toxicity of the combination vs. zorubicin as monotherapy. PATIENTS AND METHODS: A total of 80 patients entered the study. The diagnosis of UCNT was confirmed by two independent pathologists. All patients had their primary tumors in the nasopharynx. The patients were randomized in two groups: group A (zorubicin 325 mg/m2, day 1), and group B (zorubicin 250 mg/m2, day 1 and cisplatin 30 mg/m2, days 2-5). The inter-cycle interval was four weeks. The two groups were well balanced according to sex, age, stage Ho and TNM stage. RESULTS: Group A: 40 patients included, 34/40 evaluable for activity. Activity on evaluable patient basis: CR 4/34 (11.75%), PR 4/34, SD 14/34, PD 12/34, response rate 8/34 (23.5%); response rate on intent to treat basis 8/40 (20%). TOXICITY: granulocytopenia grade 3-4 6/40, thrombocytopenia grade 3-4 2/40, no febrile neutropenias, nausea/vomiting any grade 3/40, cardiac toxicity any grade (rhythm) 3/40 other toxicities minor or absent. Group B: 40 patients included, 36/40 evaluable for activity. Activity on evaluable patient basis: CR 10/36 (27.78%), PR 17/36, SD 3/36, PD 6/36, response rate 27/36 (75%); response rate on intent to treat basis 27/40 (67.5%). TOXICITY: granulocytopenia grade 3-4 10/40, thrombocytopenia grade 3-4 8/40, two febrile neutropenias, nausea/vomiting any grade 13/40, other toxicities mild or absent. Of the group of patients achieving a CR, four relapsed following 7, 11, 22 and 23 months, one was lost to follow-up, one died after six months from fulminant hepatitis B and eight are in complete remission lasting for 30+ to 66+ months. Following CR achievement none received any consolidation radiotherapy, and the projected five years of freedom from relapse for complete responders is about 60%. CONCLUSION: Zorubicin is an effective drug in UCNT and its combination with cisplatin has a significant activity and an acceptable toxicity.

[Levels of immune complexes in fresh and frozen serum and plasma detected by precipitation with polyethylene glycol in patients with malignant diseases]. / Razlicite kolicine imunskih kompleksa u svezem i zamrznutom serumu i plazmi bolesnika s malignim oboljenjem izmerene precipitacijom polietilen-glikolom.

INTRODUCTION: Immune complexes are macromolecules consisting of immunoglobulins (antibodies) bound to different antigens [1]. Determination of circulating immune complexes in patients with malignant diseases can be of some interest for prognosis and follow-up of a disease [2, 3]. According to certain data the immune complexes concentration varies in dependence of disease stage [4] and it is not affected by therapy [5]. Precipitation with polyethylenglycol is a physical method for determination of circulating immune complexes, based on the ability of high molecular polymers to precipitate macromolecules from sera [6]. This mechanism of precipitation is not yet well understood, but it is probably based on steric exclusion of water molecules that affects insolubility of immune complex molecules [7]. Repeatedly frozen sera demonstrated rapid decrease in detected concentration of circulating immune complexes [8] by polyethylenglycol. The presence of complement affects solubility of circulating immune complexes [7]. While there are no data about the influence of other proteins in sera or plasma, the aim of this study was to find out if there are any significant differences between the circulating immune complexes levels, determined by polyethylenglycol, in sera, plasma or in only once frozen sera. MATERIAL AND METHODS: Eighteen samples of plasma and sera from patients with malignancy (10 males and 8 females) were examined. Eight of them had non-Hodgkin lymphoma, 4 were with Hodgkin lymphoma, 4 with breast carcinoma and 2 with lung carcinoma. All samples were taken before starting chemotherapy. The circulating immune complexes determination was carried out immediately after the separation of plasma and sera and also in sera frozen for 10 days at -35 degrees C. Circulating immune complexes were determined spectrophotometrically. The absorbance (A450) of serum or plasma in 3.75% of polyethylene glycol, polyethylenglycol (M = 6000) solution was used as the measure of the circulating immune complexes level [9]. The standard for circulating immune complexes determination in g/l was aggregated IgG at 36 degrees C for 30 minutes from the serum of healthy volunteers. RESULTS: The mean value and the range of circulating immune complexes level (A450) are given in Table 1. The values in g/l are presented in Graph 1. The values of circulating immune complexes in plasma were significantly lower than those in fresh sera (t = 2.8125; p < 0.02). There was no significant statistic difference between levels in circulating immune complexes (A450) in fresh and frozen sera (t = 1.3261; p > 0.1). DISCUSSION: In dependence on its concentration polyethylenglycol shows the ability to precipitate proteins selectively [10]. The selectivity was tested mainly towards immunoglobulins and the complement. Results obtained in this study show statistically significant lower circulating immune complexes level in plasma than in serum or frozen serum. The main difference between sera and plasma is in complete absence of fibrinogen, factors V and VIII in sera and in presence of Ca++ ions. Besides that plasma contains an anticoagulant [11]. It is possible that the presence of fibrinogen and some coagulation factors disturb the polyethylenglycol precipitation mechanism. According to this, it might be, that mechanism, based on steric exclusion of water molecules, selectively influences polyethylenglycol precipitation of circulating immune complexes in plasma. It is difficult to say how much Ca++ ion and anticoagulant, as well as the activity of some plasma enzymes, and possible dissociation of circulating immune complexes influence the formation of precipitate. In any case, there is a significant difference between concentration of circulating immune complexes according to substrate. For that reason, it is necessary to detect circulating immune complexes by polyethylanglycol always in the same medium for exact clinical evaluation. (ABSTRACT TRUNCATED)

Serum gonadotropin levels in patients with germ-cell tumors of the testis: interrelations, possible cross-reactions and interpretation of beta-HCG level.

The concentration of FSH, LH, LTH, testosterone and beta-hCG was estimated in 177 serum samples from 86 patients with malignant germ-cell tumors of the testis. The objectives of the investigation were the following: the detection of interrelations of hypophyseal gonadotropins at different beta-hCG levels; the determination of the significance of borderline values of beta-hCG; the analysis of the effect of elevated concentrations of beta-hCG on pituitary gonadotropins: the detection of possible cross-reactions during gonadotropin determinations. The RIA method was used to estimate levels of three gonadotropins. The results revealed that there was no cross-reaction between FSH and beta-hCG at RIA assays. When the serum level of beta-hCG of tumor origin exceeded 100 U/l a subtotal inhibition of FSH secretion was observed. Pathologically increased values of beta-hCG were found not only in serum with subnormal-FSH levels, but also when FSH levels were excessively elevated (exceeding 50 U/l). In the latter case the elevated beta-hCG levels could possibly be the consequence of the secretion of beta subunits by the hypophysis or a cross-reaction with LH, and not of a tumor. With values of beta-hCG over 100 U/l cross-reaction with LH occurs, so the true LH levels cannot be assessed. For an adequate interpretation of elevated values of beta-hCG in the serum (i.e. whether they are tumor-derived or not), it is necessary to have values of FSH from the same serum sample.

Randomised study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma.

A randomised study was started in chemotherapy-naive patients with advanced soft tissue sarcomas who received either epirubicin 60 mg/m2/24 h (total dose for cycle 180 mg/m2) days 1, 2 and 3, (group A) or epirubicin 60 mg/m2/24 h days 1, 2 and 3 and cisplatin 30 mg/m2/24 h days 2, 3, 4 and 5 (group B). The maximal number of cycles foreseen in both groups was eight. Cardiotoxicity of the regimens was monitored by serial LVEF determinations. 106 patients entered this study, 50 (45 evaluable for activity) randomised to group A, and 56 (54 evaluable for activity) to group B. The groups were well balanced for age, sex, performance status and histological type. In group A, there was 1 complete response (CR) and 12 partial responses (PR), the overall response being 13/45 (29%); in group B, there were 7 CRs and 22 PRs, the overall response being 29/54 (54%). The difference between the overall response was statistically significant (chi 2 = 6.19, P < 0.025). The epirubicin-cisplatin regimen was found to be more toxic for platelets and more emetogenic, but cardiotoxicity, either acute or cumulative, was not found to be a major problem in both groups. However, a complete responder receiving a cumulative epirubicin dose of 1440 mg/m2 died from congestive heart failure after a disease-free interval of 27 months. The high response in group B could be the result of the synergism between high-dose epirubicin and cisplatin in patients with advanced soft tissue sarcomas.

Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia.

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

[Mechanisms in onset of postoperative immunodepression and its importance in the surgical treatment of cancer patients]. / Mehanizmi nastanka postoperativne imunodepresije i njen znacaj za hirursko lecenje onkoloskih bolesnika.

Postoperative immunodepression is inevitable transient path of operative trauma. Changes in the immunologic status are related to the duration of the anesthesia and surgery procedure. Mortality and morbidity and recurrence rate may be related with immunodepression.

[A pilot study of high-dose zorubicin in advanced stages of soft tissue sarcoma in adults]. / Etude pilote de la zorubicine à hautes doses dans les stades avancés des sarcomes des tissus mous de l'adulte.

High-dose anthracyclines, doxorubicin 75 mg/m2 and epirubicin 150-180 mg/m2, are the most active drugs in the treatment of advanced soft tissue sarcoma. These dosages are associated with significant hematological toxicity for both drugs and a high risk of cardiotoxicity for doxorubicin. The aim of this pilot study was to investigate the activity of zorubicin in advanced soft tissue sarcoma, with a dosage supposed to be equihematotoxic to epirubicin 180 mg/m2. Twenty of 21 patients who had been included in the study were evaluable for response, 15 males and five females, median age 41 (range 20-67) years. All patients received zorubicin 600 mg/m2 per cycle divided in 3 days, the intercycle interval being 4 weeks. The cardiac function was monitored by determinations of left ventricular ejection fraction before each cycle. Therapeutic response was the following: 2/20 patients (10%) complete response, 6/20 (30%) partial response, 6/20 (30%) stable disease and 6/20 (30%) progressive disease, the overall response rate being 8/20 (40%). Complete responses were observed in a patient with undifferentiated sarcoma of the mediastinum and in a patient with unresectable angiosarcoma of subcutaneous tissues. The major toxicity was hematological, with granulocytopenia grade 4 occurring in 42/66 cycles, and the nadir on day 10 of the treatment cycle. Nine of 66 cycles were complicated by febrile neutropenia and stomatitis of any grade was recorded in only 1/66 cycles. No cumulative cardiotoxicity was observed up to a total cumulative zorubicin dose of 3,000 mg/m2.

Modulation of cisplatin antitumor activity by short infusional high-dose cytosine arabinoside in advanced pretreated head and neck carcinoma: a phase II study.

The aim of the present study, which included 24 pretreated patients (both with radiotherapy and/or cisplatin-containing chemotherapy) with histological grade I/II head and neck cancer, was to investigate whether the enhancing action of cytosine arabinoside on cisplatin antitumor activity might be evidenced without excessive hematological toxicity with the administration of short infusional high-dose cytosine arabinoside, applied before cisplatin. Cytosine arabinoside was administered on day 1 of the treatment cycle at 0h and 12h at the dosage of 500 mg/m2 (1 hour infusion), and cisplatin at 6h and 18h of the same day with a dose of 20 mg/m2. On days 2, 3 and 4, only cisplatin 30 mg/m2/24h was administered. 19 patients were evaluable for activity including 14 patients pretreated with cisplatin-containing chemotherapy. 2/19 achieved complete response (CR), 2/19 a partial response (PR), 8/19 had stable disease and 7/19 progressive disease. Objective responses (2 CR and 1 PR) were evidenced in 3/14 patients previously resistant to cisplatin at the same dosage as in the present regimen. WHO grade IV toxicity for granulocytes was recorded in only one patient.

[Levels of certain immunologic parameters in patients with carcinoma of the epipharynx]. / Vrednosti pojedinih imunoloskih parametara kod bolesnika s carcinomom epifarinksa.

According to several histological and immunological features undifferentiated carcinoma of the nasopharynx (UCNT) is different from other ORL carcinomas (abundant lymphocytic infiltrate and frequent positive serology to EBV). Thus, immunological and virusological investigations were frequently performed in order to determine their diagnostic and prognostic significance. This study mainly concerned EBV serology and related immunological parameters. There are less data about immunological profile in those patients. In the present study, several standard immunological parameters were tested (number of different rosette-forming cells in peripheral blood, immunoglobulins serum levels and blastic transformation in the presence of PHA) in 17 patients with UCNT, 16 males and 1 female, aged 20 to 79 years. The aim of this study was to find out whether these patients were different from healthy controls, and if any of these parameters could be of prognostic value. Results point to the following disturbances in our group of patients: absolute lymphopenia caused by T-lymphopenia and significant decrease in ability of blastic transformation. Contrary to the registered suppression of cellular immunity there was a certain degree of stimulation of humoral response detected by hypergamaglobulinaemia and appearance of monoclonal immunoglobulin components in sera of few patients. All these immunological disturbances have no prognostic value in predicting the treatment response to chemotherapy.

[High-dose medroxyprogesterone acetate in the treatment of metastatic carcinoma of renal parenchyma]. / Velike doze medroksiprogesteron-acetata u lecenju metastatskog karcinoma parenhima bubrega.

In animals it was found that the growth of oestrogen induced renal cell carcinoma can be inhibited by progesterone derivatives. In human clinical studies of metastatic renal cell carcinoma treated with MPA doses of 500 mg/24 h the overall response was about or below 10%. However, it has been noted that there is a dose effect relationship in MPA in breast cancer. As the level of hormonal receptors in renal cell carcinoma tissue is low, it could be expected that dose escalation of MPA might influence the therapeutic response. Thirteen patients with metastatic renal cell carcinoma with progressive disease treated with MPA doses of 500 mg/24 h were treated with escalated doses of MPA 2000 mg/24 h for 10-15 consecutive days, the drug free interval being 3-4 weeks. Twelve patients were evaluated for response. Partial response was registered in 3/12 patients with median survival-time of 15 months, 4/12 patients had stable disease and 5/12 patients had progressive disease. All patients with a partial response have been previously nephrectomised, and had lung metastases. The type of the response was also noted in interferon treated patients. During the high-dose MPA treatment several patients displayed thrombocytopenia, a phenomenon difficult to interpret. One patient, previously nephrectomised, developed fatal renal vein thrombosis of the remaining kidney. Other toxic effects (weight gain, transitory psychotic episodes) did not require treatment interruption. There seems to be a dose response relationship of MPA in a sub-category of patients with metastatic renal cell carcinoma, and additional treatment responses may be observed in patients treated with escalated MPA doses.

[Anti-pain effect of salmon calcitonin in bone metastases of malignant tumors with the exception of breast and prostatic carcinoma]. / Ispitivanje antidolorozne aktivnosti lososovog kalcitonina u kostnim metastazama malignih tumora iskljucujuci karcinom dojke i karcinom prostate.

In 16 patients with pain caused by diffuse osteolytic or osteoplastic-osteolytic metastases, salmon calcitonin was used as pain relieving treatment. All patients were pretreated with opiate type analgesics without a satisfactory effect. In 2 patients it was possible to withdraw completely previous opiate intake. In most of the patients the analgesic effect of salmon calcitonin consisted in decrease of pain with identical or decreased intake of opiate type analgesics. In 3 patients the pain relieving treatment with salmon calcitonin completely failed. Our investigation seems to demonstrate that there is a subpopulation of patients with bone metastases, resistant to opiate type analgesics, in which salmon calcitonin can be administered as an additional useful pain relieving drug.