COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases.

BACKGROUND: COVID-19 has significantly affected patients with cancer and revealed unanticipated challenges in securing optimal cancer care across different disciplines. The European Society for Medical Oncology COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international, real-world database, collecting data on the natural history, management, and outcomes of patients with cancer and SARS-CoV-2 infection. METHODS: This is the 2nd CoCARE analysis, jointly with Belgian (Belgian Society of Medical Oncology, BSMO) and Portuguese (Portuguese Society of Medical Oncology, PSMO) registries, with data from January 2020 to December 2021. The aim is to identify significant prognostic factors for COVID-19 hospitalization and mortality (primary outcomes), as well as intensive care unit admission and overall survival (OS) (secondary outcomes). Subgroup analyses by pandemic phase and vaccination status were carried out. RESULTS: The cohort includes 3294 patients (CoCARE: 2049; BSMO: 928, all hospitalized by eligibility criteria; PSMO: 317), diagnosed in four distinct pandemic phases (January to May 2020: 36%; June to September 2020: 9%; October 2020 to February 2021: 41%; March to December 2021: 12%). COVID-19 hospitalization rate was 54% (CoCARE/PSMO), ICU admission 14%, and COVID-19 mortality 22% (all data). At a 6-month median follow-up, 1013 deaths were recorded with 73% 3-month OS rate. No significant change was observed in COVID-19 mortality among hospitalized patients across the four pandemic phases (30%-33%). Hospitalizations and ICU admission decreased significantly (from 78% to 34% and 16% to 10%, respectively). Among 1522 patients with known vaccination status at COVID-19 diagnosis, 70% were non-vaccinated, 24% had incomplete vaccination, and 7% complete vaccination. Complete vaccination had a protective effect on hospitalization (odds ratio = 0.24; 95% confidence interval [0.14-0.38]), ICU admission (odds ratio = 0.29 [0.09-0.94]), and OS (hazard ratio = 0.39 [0.20-0.76]). In multivariable analyses, COVID-19 hospitalization was associated with patient/cancer characteristics, the first pandemic phase, the presence of COVID-19-related symptoms or inflammatory biomarkers, whereas COVID-19 mortality was significantly higher in symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status ≥2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage. CONCLUSIONS: The updated CoCARE analysis, jointly with BSMO and PSMO, highlights factors that significantly affect COVID-19 outcomes, providing actionable clues for further reducing mortality.

COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE).

BACKGROUND: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). PATIENTS AND METHODS: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. RESULTS: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI) <25 kg/m2, presence of comorbidities, symptomatic disease, as well as haematological malignancies, active/progressive cancer, neutrophil-to-lymphocyte ratio (NLR) ≥6 and OnCovid Inflammatory Score ≤40 were associated with COVID-19 severity (i.e. severe/moderate disease requiring hospitalization). About 98% of patients with mild COVID-19 recovered, as opposed to 71% with severe/moderate disease. Advanced cancer stage was an additional adverse prognostic factor for recovery. At data cut-off, and with median follow-up of 3 months, the COVID-19-related death rate was 24.5% (297/1212), with 380 deaths recorded in total. Almost all factors associated with COVID-19 severity, except for BMI and NLR, were also predictive of inferior OS, along with smoking and non-Asian ethnicity. CONCLUSIONS: Selected patient and cancer characteristics related to sex, ethnicity, poor fitness, comorbidities, inflammation and active malignancy predict for severe/moderate disease and adverse outcomes from COVID-19 in patients with cancer.

Metabolic activity of breast cancer metastatic lesions on positron emission tomography/computed tomography: comparison with histological and biological characteristics of primary tumor.

Higher intensity of FDG uptake on PET/CT in primary tumor is seen in patients with IDC compared to ILC, also in high grade tumours, tumours with negative ER and higher Ki67 values, while data are inconsistent in case of relation between primary tumor's PgR and HER2 expression with its metabolic activity levels. On account of the lack of studies that include research of breast cancer metastatic lesion metabolism level and its relation to tumor histology and biology, our goal was to investigate the association of metastatic lesions' glucose metabolism level on PET/CT with different histological and biological characteristics of primary tumor. In a total number of N=100 patients, highest SUVmax values for each patient were used in testing difference between metastatic metabolic activity in patients with different tumor histology, grade, ER, PgR and HER2 status, subtype, as well in testing relation of Ki67 index to metastasis' metabolism level. In testing difference between histological types of breast cancer, SUVmax values were also compared separately for each specific anatomical site (regional and distant lymph nodes, bones and liver). No difference was found regarding metastatic SUVmax values in patients with primary IDC (n=55, median SUVmax 9.70) and ILC (n=34, median SUVmax 7.20) independently of anatomic site, and for each of analysed sites separately. No difference was found as well between SUVmax detected in metastasis in patients with different grade (grade II: n=58, median SUVmax 7.70; grade III: n=12, median SUVmax 10.20), ER (59 positive, median SUVmax 8.50; 22 negative, median SUVmax 8.05), PgR (55 positive, median SUVmax 8.50; 23 negative, median SUVmax 7.80), and HER2 (14 positive, median SUVmax 6.84; 51 negative, median SUVmax 8.63) expression in primary tumor, and between patients with different tumor subtype. Ki67 was also not associated with tumor metastatic SUVmax values (n=11, rs = -0.21, p=0.53). We conclude that there is no association of primary breast cancer histological type, grade, ER, PgR, HER2 and Ki67 expression with metabolic activity in metastasis detected on PET/CT.

PTEN protein expression in postmenopausal steroid receptor positive early breast cancer patients treated with adjuvant tamoxifen.

PURPOSE: Since one of possible causes of resistance to antiestrogen therapy in steroid receptor positive (SR+) breast cancer (BC) patients is an alteration of PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways, the aim of this study was to determine the PTEN protein expression in postmenopausal patients with steroid SR+ BC treated with adjuvant tamoxifen, to investigate the association of PTEN protein expression with tumor histology, size and grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) statuses and disease outcome. METHODS: This was a retrospective analysis of 78 postmenopausal stage I/II SR(+)BC patients treated with adjuvant tamoxifen. PTEN protein expression and ER, PR and HER2 status were determined using immunohistochemistry. RESULTS: The distribution of PTEN protein expression according to tumor histology was as follows: PTEN+ status in 27/43 (62.8%) patients with ductal and in 26/35 (74.3%) patients with lobular carcinomas; and PTEN(-) status in 16/43 (37.2%) patients with ductal and in 9/35 (25.7%) patients with lobular carcinomas. Disease relapse was observed in 38/78 patients: 14/53 (26.4%) of PTEN(+) BC subgroup and 24/25 (96%) of PTEN(-) subgroup (x(2), p=0.018). There were no significant associations between PTEN protein expression and tumor histology, size and grade, and ER, PR and HER2 expression. Patients with PTEN(-) had significantly shorter disease-free interval (DFI) and overall survival (OS) (for both, log rank test, p <0.01) compared to PTEN(+) BC patients. CONCLUSION: Our results suggest that PTEN protein expression might be of prognostic significance in postmenopausal SR(+) BC patients treated with adjuvant tamoxifen.

Dose-finding study of capecitabine in combination with weekly paclitaxel for patients with anthracycline-pretreated metastatic breast cancer.

PURPOSE: Capecitabine and paclitaxel show high efficacy, non-overlapping toxicity profiles and preclinical synergism, providing the rationale for their combination in metastatic breast cancer (MBC). This dose-escalation study aimed at determining the maximum tolerated dose (MTD) of capecitabine plus paclitaxel in anthracycline-pretreated MBC patients. PATIENTS AND METHODS: Patients with MBC received fl at-dose of oral capecitabine (1,000 mg/m(2) twice daily, days 1-14) plus weekly paclitaxel 60, 75, or 90 mg/m(2), i.v., days 1, 8 and 15, every 3 weeks. RESULTS: All 11 patients enrolled onto study were evaluable for toxicity and response. Two patients receiving paclitaxel 75 mg/m(2) experienced grade 3 nail toxicity, with grade 3 hand-foot syndrome (HFS) in one patient and grade 2 dermatitis in the other. Although not life-threatening, these were considered unacceptable and the preceding dose level was selected. Eight of 11 patients achieved objective responses. CONCLUSION: The recommended regimen is capecitabine 1,000 mg/m(2) twice daily, days 1-14, plus paclitaxel 60 mg/m(2)/week. Escalation of the paclitaxel dose above 60 mg/m(2)/week is not feasible due to severe skin toxicity.

Postmastectomy radiotherapy in intermediate risk stage I-II breast cancer patients.

PURPOSE: To evaluate the correlation of postmastectomy radiotherapy (PMRT) with local relapse rate, disease-free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients at intermediate risk for locoregional relapse (stage I-II with either 1-3 positive axillary nodes, or node-negative grade III BC) treated with radical mastectomy. PATIENTS AND METHODS: We evaluated 482 stage I-II BC patients, with either node-negative grade 3 tumors or with 1-3 positive nodes irrespective of tumor grade, treated with radical mastectomy at our Institute from 1986 to 1994. After mastectomy they received either adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (N=172), or adjuvant endocrine therapy (N=310). Postoperative radiotherapy (RT group) to the regional lymph nodes with tumor dose (TD) 48 Gy in 22 fractions was delivered to 199 patients. RESULTS: After a median follow-up of 79.5 months, no difference in relapse rate between the two groups was seen (30.6% in the RT group vs. 36.7% in the no RT group; x(2), p=0.1). Local recurrence rate occurring alone or with distant metastases was 4.52% in the RT group vs. 7.77% in the no RT group (x(2), p=0.1). However, local recurrence rate alone was significantly higher in the RT group compared to the no RT group (2.01 vs. 6.01%, x(2), p=0.041). In premenopausal patients local relapses occurred in 3.2% of patients with postoperative RT and in 8.2% in patients without RT (Fisher's exact test, p=0.48). Non significant difference was registered in postmenopausal patients with (4.76%) or without RT (6.58%). Ten-year DFS and OS were 53.5% and 68.7% in the RT group vs. 52.9% and 75.2% in the no RT group (non significant difference). CONCLUSION: Our results did not show that PMRT significantly influences the incidence of disease relapse, DFS and OS in stage I-II BC patients with intermediate risk for disease relapse. However, it seems that PMRT might influence the occurrence of locoregional recurrence in these patients.

Primarily tamoxifen-unresponsive, steroid receptor-positive breast cancer may respond to an aromatase inhibition: a pilot study.

PURPOSE: Breast carcinomas becoming tamoxifen-resistant after objective clinical response to antiestrogen therapy may remain responsive to other endocrine agents due to different mechanisms of action. The aim of our study was to analyze whether primarily tamoxifen-unresponsive/steroid receptor (SR) - positive breast carcinomas can respond to an aromatase inhibition. PATIENTS AND METHODS: Thirteen postmenopausal, SR-positive, metastatic breast cancer (MBC) patients were included: they had previously failed to respond to tamoxifen, either as primary systemic therapy for advanced disease, or as adjuvant treatment (5 and 8 patients, respectively). Patients were treated with 2.5 mg letrozole daily, from 2-25 months, mostly until disease progression. RESULTS: Partial response (PR) was obtained in one third of the patients (4/13); additionally, 3 patients showed disease stabilization (SD) longer than 6 months. The observed response duration lasted from 7 to 36+ months (median 9). Overall survival from the beginning of letrozole treatment was better in letrozole responders compared with nonresponders. It appeared as if there were two different subgroups of patients: one completely endocrine-unresponsive, and the other unresponsive to tamoxifen but responsive to letrozole (supposed to be primarily tamoxifen-resistant, but otherwise endocrine-responsive). HER-2 overexpression (immunohistochemically determined as 2+ and 3+) was found in 3 patients, which could not account for the different endocrine responsiveness. CONCLUSION: Our study confirmed that some SR-positive breast carcinomas, primarily tamoxifen-unresponsive, may respond to letrozole, thus being endocrine-responsive, while others did not respond, probably due to complete endocrine unresponsiveness. It is not likely that HER-2 was the biomarker that made the difference between these two subgroups.

The influence of steroid receptors status on disease outcome in early breast cancer patients treated with adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy.

PURPOSE: To assess the influence of steroid receptors (SR) status on disease outcome of early breast cancer patients treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy. PATIENTS AND METHODS: Sixty-six node-negative patients with grade 3 invasive breast carcinoma and 95 patients with 1-3 involved axillary lymph nodes regardless of tumor grade received adjuvant CMF chemotherapy. The endpoints of this analysis were disease-free survival (DFS) and overall survival (OS). Statistical analysis included log rank test and Cox regression models. RESULTS: The median follow-up period was 81 months (range 6-208). Patients with progesterone receptor (PR) - negative tumors had better DFS compared to women with PR-positive tumors (log rank test, p=0.033). Estrogen receptor (ER) - negative and PR-negative patients in the node-negative subgroup had better DFS than ER-positive and PR-positive patients (for ER: log rank test, p=0.009, and for PR: log rank test, p=0.004). However, positive lymph nodes were the only significant predictor of disease progression among patients receiving CMF therapy (Likelihood Ratio test, p <0.001). Women under 40 bearing SR-positive breast cancer had a trend toward worse DFS (log rank test, p=0.054) compared to older SR-positive premenopausal women. CONCLUSION: We can not unequivocally reveal the influence of SR status on disease outcome in early breast cancer patients treated with adjuvant CMF, although SR-positive patients in the node-negative group were shown to have worse DFS in comparison to SR-negative ones. However, nodal status remained the only independent predictor of disease progression in these patients.

Gabapentin for relief of neuropathic pain related to anticancer treatment: a preliminary study.

The aim of our study was to explore a potential analgesic effect of gabapentin in patients with neuropathic pain caused by anticancer treatment. A total of 23 outpatients without active disease and with chronic, treatment-related pain were included in this single-center, open-label, exploratory, non-controlled study. The primary end-points were pain intensity and pain relief following a 4-week treatment period. A total of 15 patients (65%) completed the study, 5 (22%) discontinued the study due to treatment failure and 3 (13%) due to toxicity. More than 50% reduction in pain intensity was obtained in 11 of 23 patients (48%, 95% CI 30-66%). Pain relief increased from 8.33% (+/- 13.64) to 66.58% (+/- 18.35) (p <0.01). Somnolence, mental clouding, and headache were the most frequently reported adverse events. We concluded that gabapentin should be accepted for further investigation in this important setting of supportive care.

High efficacy of a single oral dose of ondansetron 8 mg versus a metoclopramide regimen in the prevention of acute emesis induced by fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy for breast cancer.

The aim of our single-center, prospective, randomized, open study was to evaluate the antiemetic efficacy and tolerability of a regimen based on a single oral dose of ondansetron 8 mg in comparison with a metoclopramide-based regimen, for prevention of acute FAC (fluorouracil, doxorubicin and cyclophosphamide) chemotherapy-induced emesis. A total of 149 chemotherapy-naive, female outpatients, under 50 years of age and with no history of alcohol consumption, scheduled to receive their first cycle of FAC chemotherapy, were included. The patients received either oral ondansetron (8 mg) or metoclopramide (1.5 mg/kg, i.v.), both combined with dexamethasone (16 mg, i.v.) and alprazolam (0.5 mg t.i.d. orally). No antiemetic prophylaxis was given for delayed emesis. Complete control of acute vomiting was obtained in 69/74 (93%) of patients receiving ondansetron, and in 49/75 (65%) of those receiving metoclopramide (p=0.00003). Complete control of acute nausea was obtained in 58% of patients receiving ondansetron and in 36% of those receiving metoclopramide (p=0.007). Complete prevention of delayed vomiting/nausea was achieved in 73%/20% and 60%/16% of patients, respectively. Sedation was more frequent in the metoclopramide arm (p=0.04). As far as we know this is the first study that supports the efficacy of a regimen based on a single oral dose of ondansetron 8 mg in the prevention of acute FAC chemotherapy-induced emesis. The ondansetron regimen was highly effective in female patients and was superior to the metoclopramide based regimen.

Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer.

This retrospective study was undertaken in order to assess the prognostic value of prechemotherapy serum CA125 level, CA125 kinetics, and CA125 half-life compared to the ten common clinicopathological variables in patients with advanced ovarian cancer (AOC). CA125 serum levels were determined before and during induction cisplatin polychemotherapy in 222 patients. A prechemotherapy CA125 level higher than 35 U/mL was found in 134 patients. Blood samples were further obtained before each course of chemotherapy (CT). CA125 half-life values were calculated in 112 patients with CA125 levels above 60 U/mL using van der Burg's exponential regression model. The prechemotherapy CA125 level had no prognostic value for survival. However, the median survival time of patients with CA125 levels below the upper normal limit of normality after two courses of CT was 101 months compared to a median survival of 21 months in patients without CA125 normalization (p=0.0000). Half-life calculation showed a significant correlation with survival. The median survival times of patients with T1/2 <20 days and T1/2 >20 days were 101+ and 18 months, respectively (p=0.0003). In a survival analysis using the Cox proportional hazard model, independent prognostic variables for survival included therapeutic response (p<0.0001), Karnofsky index (p<0.0001), residual disease (p<0.0001), tumor grade (p=0.0002), CA125 half-life (p=0.007), and CA125 kinetics (p=0.04). As a consequence, the possibility to predict treatment response by the CA125 half-life during chemotherapy and the time needed for normalization of CA125 levels can divide patients into good and poor prognostic groups early during chemotherapy.

Radio- and chemotherapy variably affect the general immunocompetence of lung cancer patients.

OBJECTIVE: The evaluation of the effects of radiotherapy and chemotherapy on the immune status of lung cancer patients. EXPERIMENTAL DESIGN: Prospective nonrandomized study. SETTING: Hospitalized care. PATIENTS: 121 patients with unresectable non-small-cell lung cancer (Stage IIIb or IV), who were planned for radiotherapy (n = 81) or chemotherapy (n = 40). MEASURES: The relative and absolute numbers of blood T lymphocytes and monocytes, as well as the mitogen-induced proliferative response of the former, and phagocyting capacity of the latter cell subpopulation, were determined in patients before starting any therapy. In radiotherapy (RT)-treated group, the immune parameters were evaluated after 45 Gy and 60 Gy had been given. In chemotherapy (ChT)-treated group, the same parameters were determined three weeks after the 2nd and 4th cycle of ChT. RESULTS: The number and proliferative response of T lymphocytes were significantly (p < 0.001) lower, while the number and phagocyting capacity of monocytes were significantly (p < 0.001) higher in all patients before therapy, in comparison to the controls. After RT, the T cell number and proliferative response were significantly (p < 0.001) decreased, while the number of monocytes and their phagocyting capacity remained unchanged, when compared to the pretreatment values. Unlike RT, chemotherapy did not change any investigated parameter, except for the phagocyting activity of monocytes, which was significantly (p < 0.02) decreased, in comparison to the pretreatment value, after four cycles of ChT only. CONCLUSIONS: Two cancer treatment modalities--radio- and chemotherapy--variably affect the immune status of lung cancer patients. The initial great disturbances of general immunity parameters are further aggravated by radiotherapy. Unlike RT, chemotherapy exerts no suppression at all; on the contrary, it tends to normalize some of the parameters of cellular immunity of lung cancer patients.

Mitoxantrone, 5-fluorouracil and low-dose leucovorin in doxorubicin-resistant advanced breast cancer patients: a phase II study.

AIM: Twenty-two anthracycline-resistant advanced breast cancer patients were entered from June 1995 till November 1997 in a phase II study to assess the activity and tolerability of second-line chemotherapy consisting of mitoxantrone, 5-fluorouracil and low-dose leucovorin. STUDY DESIGN: Patients were eligible if they failed to respond to doxorubicin-containing chemotherapy, given as first-line chemotherapy for metastatic disease. Treatment consisted of mitoxantrone, 12 mg/m2 iv infusion on day 1, and leucovorin, 50 mg iv 1 hr before 5-fluorouracil, 350 mg/m2 iv infusion on days 1-3, every three weeks. RESULTS: Nineteen patients were eligible for response, 2 refused further therapy after 2 cycles, and 1 was excluded because grade 3 myelotoxicity developed during the first cycle. Partial remission of 15 months duration occurred in 1 patient, in 7/19 women disease remained stable with a median duration of 11 months (range, 5-24), and 11/19 patients experienced progressive disease. Median time to disease progression was 2 months (range, 0-17), and median survival was 8 months (range, 0-24). Toxicity was generally mild and acceptable. One patient was excluded because of grade 3 granulocytopenia and thrombocytopenia, and one due to cardiotoxicity assessed by the drop of left ventricular ejection fraction to more than 20% below the initial value. CONCLUSIONS: In spite of the very low objective response rate, almost one-fourth of our anthracycline-resistant patients achieved a disease stabilization of 27 weeks duration during mitoxantrone-based second-line chemotherapy. Hence, mitoxantrone in combination with 5-fluorouracil, especially continuous infusion, should be further investigated in this setting, particularly if new and expensive drugs, considered the most active, are not readily available.

Vitamin C inhibits random migration of malignant pleural effusion mononuclear cells.

Although many epidemiological studies indicate protective effect of vitamin C against a variety of human malignancies its mechanism(s) of action is questionable. The presented results show that the part of its effect may be accomplished by mononuclear cells, as necessary participants in body defence. Namely, in a long-term in vitro assay we tested vitamin C influence on random migration ability of malignant pleural effusion mononuclears (PEM) obtained from breast cancer patients. Vitamin C in a dose- (50-500 micrograms) and time-dependent (4-44 h) manner inhibited PEM motility, suggesting that immobilization of cells in situ may contribute to its beneficial effect in human cancers.

Assessment of early epirubicin cardiotoxicity in women with breast cancer.

BACKGROUND: Anthracycline-containing chemotherapy has been the most frequently observed cause of iatrogenic cardiac damage in patients with breast cancer. The purpose of this study was to evaluate by radionuclide ventriculography whether a mean cumulative dose of epirubicin (MCDE) induced left ventricular (LV) systolic or/and diastolic dysfunction in 32 patients treated for breast cancer. MATERIALS AND METHODS: Thirty-two patients with breast cancer according to chemotherapeutical trials received MCDE of 360 m/m2. All patients were studied before and after they completed chemotherapy with radionuclide ventriculography at rest. Systolic and diastolic left ventricular parameters were assessed. RESULTS: Diastolic left ventricular parameters and R-R intervals significantly differed before and after completed chemotherapy in our patients: peak filling rate (PFR: 2.8 +/- 0.6 vs. 2.2 +/- 0.7 EDV/sec) and time to filling rate (TPFR: 182 +/- 48 vs. 2.25 +/- 50 msec), R-R: 723 +/- 51 vs. 620 +/- 45 msec, p < 0.01. Ejection fraction, as a systolic parameter/did not significantly differ before and after completed chemotherapy (EF: 59 +/- 7 vs. 58 +/- 6%), p > 0.05. CONCLUSION: Our results indicate that left ventricular diastolic dysfunction even at an MCDE of 360 mg/m2 may be an early sign of epirubicin cardiotoxicity.

[Immunomodulating effect of thymus protein fraction on disorders of general immunity in patients with lung carcinoma]. / Imunomodulatorna dejstva proteinske frakcije timusa na poremecaj opste imunosti u bolesnika sa karcinomom pluca.

The parameters of both cellular and humoral non-specific immunity were evaluated in non-small lung cancer patients (n = 26) prior to therapy, in 13 of them after radiotherapy (45 Gy in 22 fractions) and in 13 patients after combined radio-and immunotherapy (Thymex L, 1800 mg in 12 injections á 150 mg i.m., three times a week). Several parameters of general immunocompetence were altered in patients even before any therapy. The radiotherapy caused more severe immunologic disturbances, the cellular immunity being affected more profoundly. Thymex L., when given simultaneously with radiotherapy, prevented this deterioration in a majority of patients.