THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

CONTEXT: The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. OBJECTIVE: The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. DESIGN: The research is designed as a cross-sectional prospective study. PATIENTS AND METHOD: The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. RESULTS: 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). CONCLUSION: A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Glucose and lipid abnormalities in patients with adrenal incidentalomas.

Adrenal incidentalomas (AI), defined as masses detected during imaging procedures of non-adrenal disorders, have become a common clinical problem that appear to have impairment of glucose and lipid metabolism. PATIENTS AND METHODS: One hundred and ten patients (mean 53.5 age; 24-72), who were diagnosed with functioning and non-functioning AI, were assessed. Patients with hormone-secreting AI underwent biochemical evaluation regarding metabolic disorders. Data about hormone status (cortisol profile and DEX screening test), lipid profile, glycemia, insulinemia were evaluated. RESULTS: This prospective study included 41 (37.28%) patients with non-functional and 69 (62.72%) with functional AI. Tumors associated with (sub)clinical Cushing's syndrome (functional AI) are considered to have higher cortisol concentration at 8h (p=0.027), 16h (p=0.025) and after DEX screening (p<0.010), compared to the controls. Patients with cortisol-secreting AI have significantly higher concentrations of cholesterol (p=0.040), triglycerides (p=0.027) and insulin (p<0.01) than controls. The patients with metabolic disorders have a significantly higher total cholesterol, triglyceride and insulin concentration (p<0.001) compared to controls. There was significant positive correlation between cortisol concentration after DEX screening and total cholesterol (r=0.727, p=0.007), triglycerides (r=0.564, p=0.041) and insulin (r=0.957, p=0.043) in the group with metabolic disorders. CONCLUSION: The present study demonstrates the patients with functional AI have significantly higher lipid, glucose and insulin concentration than controls. There was a significant positive correlation between metabolic parameters and cortisol concentration.

A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems.

BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 µg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.

Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies.

BACKGROUND: We evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis (CVCrT). PATIENTS AND METHODS: Consecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC. RESULTS: A total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive. CONCLUSIONS: In this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.

Celiac plexus block: injectate spread and pain relief in patients with regional anatomic distortions.

BACKGROUND: The success of the neurolytic celiac plexus block, despite different approaches and methods used, depends on adequate spread of the injectate in the celiac area. This retrospective study was conducted to evaluate the patterns of alcohol spread and pain relief in patients with cancer or therapy-related anatomic distortion of the celiac area. METHODS: From 177 cancer patients who underwent computed tomography (CT)-guided single-needle neurolytic celiac plexus block via an anterior approach, a radiologist, blind to the aim of the study, retrospectively selected 105 patients with abnormal anatomy of the celiac area as judged by CT images obtained before the block. To evaluate CT patterns of neurolytic (mixed with contrast) spread, the celiac area was divided on the frontal plane into four quadrants: upper right and left and lower right and left, as related to the celiac artery. Results were expressed as the number of quadrants into which contrast spread, ie., four, three, two, or one quadrants with contrast. The patterns of contrast spread according to the number of quadrants with anatomic distortion were analyzed. Patient assessment by visual analog scale was reviewed to evaluate the degree of pain relief. Pain relief 30 days after block was considered long-lasting. Pain relief at 30 days after block was analyzed according to the number of quadrants with contrast. RESULTS: Overall, four, three, two, and one quadrants with contrast were observed in 9 (8%), 21 (20%), 49 (47%), and 26 (25%) patients, respectively. An inverse correlation was observed between the number of quadrants with anatomic distortion and the number of quadrants with contrast (P < 0.001). Long-lasting pain relief was noticed in nine of nine patients (100%; 95% confidence interval, 66-100) with contrast in four-quadrants, and in 10 of 21 patients (48%; 95% confidence interval, 26-70) with contrast in 3 quadrants (P < 0.01). None of the 75 patients with contrast in two quadrants or one quadrant experienced long-lasting pain relief. CONCLUSIONS: These findings suggest that, using the single-needle anterior approach, the neurolytic spread in the celiac area is highly hampered by the regional anatomic alterations. It also appears that only a complete (four quadrants) neurolytic spread in the celiac area can guarantee long-lasting analgesia, and that this picture may be obtained in a very limited fraction of patients with regional anatomic alterations.

The effects of excitatory amino acids on isolated gut segments of the rat.

Glutamate and aspartate are excitatory neurotransmitters in both central and peripheral nervous systems, acting on ionotropic and metabotropic receptors. In our study we have examined the effects of glutamate, aspartate, N-methyl-d-aspartate (NMDA), kainic acid and (+/-)-1-aminocyclopentane-cis-1,3-dicarboxylic acid (ACPD) on tone and spontaneous activity of isolated rat gastric fundus, jejunum, ileum, ascending colon and rectum. Both glutamate and aspartate produced concentration-dependent tonic contractions of rat fundus and rectum; the other gut segments used in the study were not responsive. While only NMDA and kainic acid produced concentration-dependent tonic contractions of isolated rat gastric fundus, all three type-selective agonists of glutamate receptors (NMDA, kainic acid and ACPD) produced tonic contractions of isolated rat rectum. The results of our study suggest that glutamate and aspartate in rat gastric fundus activate excitatory intrinsic neurons through only ionotropic receptors (NMDA and non-NMDA receptors), while the same action in rat rectum is mediated through both ionotropic and metabotropic receptors.

Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit.

OBJECTIVE: Our study aimed at evaluating the pharmacokinetic, cardiovascular, and metabolic effects of high-dose verapamil continuous intravenous infusion in cancer patients. DESIGN: Prospective clinical and pharmacokinetic study. SETTING: Intensive care unit of a Cancer Research Institute. PATIENTS: Nine patients (age range 31 to 57 yrs) with progressive cancer disease and without cardiovascular, renal, or hepatic dysfunctions. INTERVENTIONS: After a loading dose (0.15 mg/kg followed by 12 hrs of continuous intravenous infusion at 0.20 mg/kg/hr), the infusion rate of verapamil was increased every 24 hrs (0.25, 0.30, 0.35, and 0.40 mg/kg/hr). The highest rate was maintained for 48 hrs. Doxorubicin was given from the 60 th to the 108 th hr. Hydrochlorothiazide (25 mg/day) and potassium (36 mmol/day) were given orally. Altogether, 17 courses were completed. MEASUREMENTS AND MAIN RESULTS: Steady state concentration (C(SS) and systemic clearance of verapamil and nor-verapamil (active metabolite) for each infusion rate were calculated. Mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), PR, QT and QTc intervals, and left ventricular ejection fraction (LVEF) were measured, as well as daily body weight, blood glucose and potassium. C(SS) of verapamil and nor-verapamil increased more than proportionally to the infusion rate (p<.001). Systemic clearance of verapamil decreased over the range of the infusion rate (p<.005). MAP and HR decreased at the 12th hr (p<.001) and then plateaued. CVP increased (p<.01). The relationship between MAP, HR, CVP, and verapamil plasma concentrations was significant (r2 = .25, .14, and .35, respectively; p<.0001). LVEF did not change. Six patients (11 courses) developed junctional rhythm. Three patients (six courses) showed a PR interval increase (p<.05). Patients with junctional rhythm had higher Css of verapamil (p<.009). Overall, QT and QTc intervals increased (p<.01). A linear relationship was observed between verapamil plasma concentrations and QT intervals (r2 = .09, p<.01). Cardiovascular side effects did not determine treatment withdrawal in any patient. Body weight, blood glucose, and potassium did not show significant changes. CONCLUSIONS: Our data suggest a capacity-limited clearance of high-dose verapamil. In the absence of heart disease, following a step by step increase of the dosage, the high plasma verapamil concentrations (617 to 2970 ng/mL) produce frequent but well tolerated hemodynamic and electrocardiogram changes.

Central venous thrombosis: an early and frequent complication in cancer patients bearing long-term silastic catheter. A prospective study.

Studies on catheter-related central venous thrombosis (CRCVT) have been focused mainly on clinically evident CRCVT due to occlusive thrombi, underestimating therefore the actual thrombosis prevalence. This prospective study was aimed at evaluating prevalence, timing and evolution of thrombosis, and identifying involved veins and risk factors in cancer patients (pts) undergoing percutaneous subclavian central venous catheterization (CVC) for chemotherapy, parenteral nutrition or both. We enrolled 127 consecutive pts requiring partially or totally implanted central venous silastic catheters. The study protocol included peripheral phlebography (P) at day 8, 30 and every two months following CVC and/or when clinically indicated, along with peripheral and pullout P on catheter withdrawal. A quantitative scale was developed to evaluate thrombus grading in subclavian, innominate and cava veins. Age, sex, coagulation profile tumor histotype, metastases, therapy, catheter type, and catheter insertion side were also investigated. Only pts who underwent at least two P were evaluated, and chi 2 test was adopted for statistical analysis. Altogether, 95 pts were evaluable. CRCVT was observed in 63/95 (66%) pts. At day 8, 30 and 105 (representing the median days in which first, second and last P were performed) CRCVT was evidenced in 64%, 65% and 66% of the pts, respectively. Thrombus grading did not differ among first, second and last P. CRCVT was symptomatic in 4/63 (6%) pts. Thrombosis prevalence was higher in subclavian (97%) with respect to innominate (60%) or cava (13%) veins (p < 0.001). Thrombosis was higher in left subclavian catheters (14/16; 87.5%) than in right ones (49/79; 62%), p < 0.01. No associations were established between CRCVT and other investigated parameters. Our data show a very high actual frequency of CRCVT in cancer pts, and emphasize that first days following CVC are at the highest risk for CRCVT development. Based on our results, a study on short-term antithrombotic prophylaxis in cancer pts requiring CVC is warranted. Finally, our data indicate that left subclavian vein catheterization represents a risk factor for CRCVT.

Sensitization of rat gastrointestinal tract to acetylcholine and histamine produced by X-radiation.

Abdominal x-radiation produces both acute and chronic disturbances of gastrointestinal motility. Anaesthetized Albino-Oxford rats received one-session x-radiation (absorbed dose 10 Gy) of whole abdomen. Two hours after irradiation the rats were sacrificed and segments of their gastrointestinal tract (gastric fundus, jejunum, ileum and ascending colon, were mounted in isolated organ bath. Acetylcholine and 5-hydroxytryptamine produced tonic contractions of all gut segments, while histamine did so only with gastric fundus. While contractile effect of 5-hydroxytryptamine was not affected by x-radiation, the responses of all gut segments on acetylcholine were potentiated and shifted towards lower concentrations. After x-radiation histamine produced concentration-dependent tonic contraction of previously unresponsive jejunum and ascending colon. The results of our study suggest that x-radiation produces acute sensitization of rat gastrointestinal tract to acetylcholine and histamine.

Single-needle celiac plexus block: is needle tip position critical in patients with no regional anatomic distortions?

BACKGROUND: The "single-needle" celiac plexus block is becoming a popular technique. Despite different approaches and methods used to place the needle, the success of the block depends on adequate spread of the injectate in the celiac area. In the present retrospective study, the influence of needle tip position in relation to the celiac artery on injectate spread was evaluated. METHODS: Among 138 cancer patients subjected, via an anterior approach, to computed tomography (CT)-guided single-needle neurolytic celiac plexus block, a radiologist, blinded to the aim of the study, retrospectively selected 53 cases with normal anatomy of the celiac area as judged by CT. The decision was based on images obtained before the block. Patients were then classified into either group A (29 patients), in whom the needle tip was caudad to the celiac artery, and group B (24 patients), in whom it was cephalad. To evaluate CT patterns of neurolytic (mixed with contrast) spread, the celiac area was divided on the frontal plane into four quadrants: upper right and left and lower right and left, as related to the celiac artery. Patient assessments by visual analog scale were reviewed to evaluate the degree of pain relief. Pain relief 30 days after block was judged as long-lasting. The patterns of contrast spread in relation to the needle position and pain relief according to the number of quadrants with contrast were analyzed. RESULTS: The percentage of cases with four quadrants with contrast was higher when the needle tip was cephalad (58%, group B) than when it was caudad (14%, group A) to the celiac artery (P < 0.01). The percentage of patients with four and three quadrants with contrast was also higher in group B at 79% than in group A at 38% (P < 0.01). A significant difference in long-lasting pain relief was observed between patients with four quadrants with contrast (18 of 18, 100%; 95% confidence interval [CI], 81-100%) and patients with three quadrants with contrast (5 of 12, 42%; 95% CI, 15-72%) (P < 0.01). No patients showing two or one quadrant with contrast had long-lasting pain relief. CONCLUSIONS: These findings suggest that, when the celiac area is free from anatomic distortions, and the single-needle neurolytic celiac plexus block technique is used, the needle tip should be positioned cephalad to the celiac artery to achieve a wider neurolytic spread. It also appears that only a complete (four quadrants) neurolytic spread in the celiac area can guarantee long-lasting analgesia.

[Long-term oral administration of etoposide in the treatment of patients with advanced non-small-cell carcinoma of the lung. The second phase of a clinical study]. / Produzena oralna primena etopozida u lecenju bolesnika s napredovalim nemikrocelulnim karcinomom pluca. Druga faza klinicke studije.

Over the period from May 1989 to May 1992 thirty-four patients with advanced non-small cell lung cancer (NSCLC) were treated with prolonged administration of oral etoposide. Etoposide was administered in a dose of 50 mg/m2 a day for 21 days. Nine (26%) patients partially responded to the treatment that lasted 2-7 months (median 5 months). Median survival time was 6 months, and 1-year survival was 32%. The most common toxic events were alopecia and myelosuppression. No patient died of treatment-related toxicity. Results of this study demonstrate moderate efficiency of the prolonged administration of oral etoposide to patients with advanced NSCLC.

Central venous catheter-related thrombosis in clinically asymptomatic oncologic patients: a phlebographic study.

Fifty-seven oncologic patients with short- or long-term central venous catheters (CVCs) and without clinical signs of axillary-subclavian thrombosis were evaluated phlebographically. Different degrees of incomplete thrombosis were found in 26 patients (45.5%) and complete thrombosis, clinically silent, was found in six patients (10.5%). A fibrin sleeve around the CVC was radiologically demonstrated in 45 (78%) patients, 21 of them (46%) with negative standard venogram. Only in four patients there was no evidence of fibrin sleeve or parietal thrombosis. There were no significant differences between patients with long-term and short-term CVCs. We conclude that parietal thrombosis of the axillary-subclavian veins is a frequent event, even if there is no clinical evidence of flow obstruction and we confirm in vivo that a fibrin coating of the CVCs is present in the majority of the cases.

Antithrombin III deficiency as a risk factor for catheter-related central vein thrombosis in cancer patients.

The fibrin sleeve of venous catheters (VC) and parietal thrombi represent frequent and dangerous side-effects of central venous catheterization (CVC), due to the risk of embolism. Reduced levels of coagulation clotting factors inhibitors (such as Antithrombin III) are known to be associated with increased thrombogenic risk. The aim of this study was to evaluate the role of Antithrombin III (AT III) deficiency as a risk factor for thrombosis in cancer patients undergoing CVC. The study groups included patients with a reduced AT III activity (< 70%, 20 consecutive patients) and with normal AT III values (> 70%, 20 randomly selected patients), requiring a VC for chemotherapy and/or total parenteral nutrition. The study protocol included evaluation of Hb, PLTs, PT (INR), aPTT, Fibrinogen and AT III at days 0, 1, 3 and 8 after CVC and upon VC removal. Peripheral and pullout phlebographies were performed in all patients on catheter withdrawal. A quantitative scale was developed to evaluate both VC and parietal thrombus degree in each catheter-containing venous segment (subclavian, innominate, superior vena cava); the sum of the mean values was defined as overall thrombus. The average VC dwelling time was similar in both groups. There were no significant differences in Hb, PLTs, PT (INR), aPTT, Fibrinogen and in the remaining parameters of the study between the two groups. The group with AT III deficiency presented a higher degree of both parietal (p < 0.05) and overall thrombus (p < 0.02). Data showed a higher severity of CVC-related thrombosis in patients with AT III deficiency than in the control group. Further studies are needed to evaluate whether the therapeutically-induced normalization of AT III levels can reduce the thrombosis degree.

Time-dependent efficacy of bacterial filters and infection risk in long-term epidural catheterization.

BACKGROUND: Epidural infection represents a serious albeit infrequent complication of long-term epidural catheterization. The catheter hub is regarded as the main point of entry for microorganisms among the three possible routes (hematogenous, insertion site, hub) of microbial colonization of the inserted catheter. The current study was aimed at evaluating whether frequent changing of antimicrobial filters carries an increased risk of catheter hub contamination and the time-dependent efficacy of commonly used antimicrobial filters after prolonged use. METHODS: In the first part of the study, a microbiologic survey (skin, filter, hub, and catheter tip) was performed weekly in a group of 47 patients with cancer bearing subcutaneously tunneled catheters managed at home. Subsequently, the time-dependent efficacy of 96 micropore filters (32 Portex, 32 Sterifix-Braun, 32 Encapsulon TFX-Medical) differing in surface areas and/or composition of the filtering membrane was evaluated in a laboratory study. Filters were perfused, under the usual conditions of clinical use (flow resistance, injection pressure, temperature), every 8 h up to 60 days, with 5 ml of two different analgesic solutions, either sterile or containing 1.5 x 10(5)/ml of Streptococcus milleri I. Eight filters of each type subsequently were flushed with a S. milleri suspension (0.5 McFarland) after 7, 14, 28, and 60 days of continuous perfusion, and the resulting filtrates were cultured. RESULTS: In 16 of 19 positive hub cultures, the same microorganisms (species, biotype, antibiotype) were cultured from skin and filters. A statistically significant positive trend was found between the number of filter changes and the rate of positive hub cultures (chi 1(2) trend 5.11; P = 0.02). A high correlation coefficient was found between number of positive skin cultures and number of positive filtrates (r = 0.88; P = 0.01) and between number of positive filtrates and number of positive hub cultures (r = 0.93; P = 0.003). Cultures obtained from Portex and Sterifix-Braun filters yielded no bacterial growth (64/64) throughout the study period. Cultures from Encapsulon TFX-Medical filters showed bacterial growth 2/8 at seventh day, 7/8 at the 14th day, and 16/16 from the 28th day onward. CONCLUSIONS: Our data indicate significant correlation between the incidence of catheter hub colonization and the filter-change frequency, when the skin close to the filter-hub connection is contaminated. Our results also show that Portex and Sterifix-Braun bacterial filters, when perfused with reduced volumes at low injection pressures, maintain an unmodified antimicrobial function for at least 60 days. Based on these data, it appears clinically feasible to reduce the frequency of filter changes during long-term epidural catheterization, with a consequent possible decrease of epidural catheter colonization.

[Carboplatin-etoposide-bleomycine chemotherapy protocol in the treatment of patients with metastatic non-seminomatous germ-cell testicular tumours with good prognosis]. / Hemoterapijski protokol karboplatini-etopozid-bleomicin u lecenju bolesnika s metastatskim neseminomskim tumorima germinacionih celija testisa s dobrom prognozom.

Fifteen patients with metastatic non-seminomatous germ-cell tumours with good prognosis were treated with carboplatin-etoposide-bleomycine chemotherapy. Patients were followed-up from 8 to 56 months (median 32 months). In 13 patients there was no evidence of the disease and in 2 patients recurred, but recovered after the subsequent secondary chemotherapy (cisplatin-bleomycine-vincristine). Signs and symptoms of toxicity included alopecia in 93% of patients, nausea and vomiting in 40%, while in respect of haematological toxicity, leucopenia was observed in all 15 patients, thrombocytopenia in 80%, and decrease of haemoglobinaemia in 60% of patients. Other toxicities were not observed. Carboplatin-etoposide-bleomycine chemotherapy is effective and little toxic, but a greater number of patients and a longer follow-up are needed for definitive evaluatin of this therapy in the treatment of patients with metastatic non-seminomatous germ-cell testicular tumours with good prognosis.

[Chemotherapy protocol "8 drugs in 1 day" in patients with recurrent malignant glioma]. / Hemoterapijski protokol "osam lekova u jednom danu" kod bolesnika s recidivom malignog glioma.

22 patients with recurrent malignant gliome were treated with "8 drugs in 1 day" chemotherapy protocol. 3 patients achieved partial response, 7 achieved stable disease, while 12 had progressive disease. Median time to tumor progression for all patients was 13 weeks, while median survival time for all patients was 35 weeks. Hematological toxicities were the most common, resulting in treatment refusal in two patients. Other toxicities included gastrointestinal, nephrotoxicity and ototoxicity.

Cisplatin and 5-fluorouracil as induction chemotherapy followed by radiation therapy in metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck. A phase II study.

12 patients with metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck were treated with induction chemotherapy and radiotherapy. Median age was 54 years (range, 39-68 years) and male to female ratio was 2:1. Five (42%) patients had N3 disease and 7 (58%) had N2 disease. Induction chemotherapy consisted of cisplatin 60 mg/m2, days 1 and 2 and 5-fluorouracil (5-FU), 500 mg/m2, days 3 and 4. Cycles were repeated every 4 weeks to a total of 3 cycles. After 4 weeks rest, patients underwent radiation therapy. It was given to all possible sites of the primary tumor (nasopharynx, pyriform sinus, and the base of the tongue). The radiation therapy dosage planned to the whole neck, nasopharynx, and supraclavicular area was 45 Gy in 24 daily fractions in 5 weeks, increasing to 60-70 Gy to the metastatic site. We observed 9 (75%) complete responses and 1 (8%) partial response. 7 (58%) patients are currently with no evidence of disease. Median survival time for all patients is 36 months (range, 14+ to 56 months), while median survival time for N3 patients was 32 months (range, 26-56 months). Toxicities were predominantly mild to moderate nausea and vomiting and mucositis. This combined modality appears to be effective and feasible in treatment of metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck.

Carboplatin and etoposide in patients with advanced gastric cancer.

Thirty-six patients with advanced gastric cancer were treated with combination chemotherapy following surgery. Chemotherapy consisted of carboplatin (CBDCA) 300 mg/m2, days 1-3, and etoposide (VP 16) 100 mg/m2, days 1-5. 10/36 (28%) patients had objective response. The median duration of response was 8 months. Currently 26/36 patients have shown progressive disease at a median of 4 months. Three patients remain progression-free 7, 14, and 15 months after study entry, respectively. 26/36 patients have died and 10/26 remain alive at a median time of 16 months. Estimated survival for all patients is 7 months. Two groups of toxicities were observed: hematological and gastrointestinal. They were generally assessed as mild with only two grade 3 (ECOG) toxicities and with no grade 4 toxicity observed during this study.