Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer.

PURPOSE: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were those with SCLC who had progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m(2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 100 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support. RESULTS: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 2]). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 [73%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths. CONCLUSION: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.

5-fluorouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study.

PURPOSE: Cardiotoxicity associated with 5-fluorouracil (5FU) administration is infrequently reported in the literature, albeit case reports of acute coronary syndromes have been published. In the present study, patients undergoing 5FU chemotherapy were tested for the development of cardiac-related symptoms during its administration. PATIENTS AND METHODS: Five hundred twenty-two patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion were subjected to electrocardiogram (ECG) and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion was interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >2-fold enzyme elevation were admitted into a coronary care unit for at least 72 hours. Cases with acute myocardial infarction had to discontinue 5FU treatment. RESULTS: Overall 20 (3.8%) patients developed symptoms and/or ECG abnormalities due to 5FU. Patients with continuous 5FU infusion had a trend for higher incidence of cardiotoxicity (13/205, 6.3%) than the remaining (7/317, 2.2%; p=0.067). More specifically, increased toxicity was encountered in patients with continuous 24 h 5FU+ leucovorin (LV) infusion for 5 days compared to patients with the same schedule without LV (p <0.027) and patients with short 5FU+LV administration as well (p=0.024). Seven out of the 20 patients suffered acute myocardial infarction, 6 developed only ischemia, while ECG findings consistent with coronary vasospasm were detected in 4 patients and conduction disturbances in 3 patients (one subsequently died). CONCLUSION: The present study indicates a toxic effect of 5FU on myocardium, which is largely schedule-dependent. High level of alert is required when using this drug, while its toxic effect on the coronary endothelium and myocardium merits further investigation.

Antiemetic prophylaxis with ondansetron and methylprednisolone vs metoclopramide and methylprednisolone in mild and moderately emetogenic chemotherapy.

The purpose of the present study was to examine whether its is possible to successfully replace ondansetron (OND) with metoclopramide (MCP) in patients exposed to moderately emetogenic chemotherapy who did not experience severe nausea and vomiting while undergoing OND treatment during their first chemotherapy cycle. After switching to MCP, patients continued with this drug for three cycles, provided that they had adequate control of nausea and vomiting. Otherwise, they were switched back to OND. There were 76 patients, 60 women and 16 men, whose median age was 56 (mean 58) years. Karnofsky performance status score was 100 in 18 patients, 90 in 23, and 80 in 11 patients. No patient had previous chemotherapy. Thirty-four patients had breast cancer and received fluorouracil 500 mg/m2, epirubicin 100 500 mg/m2, and cyclophosphamide 500 mg/m2. Twelve patients had small cell lung cancer and received carboplatin 400 mg/m2 + etoposide 120 mg/m2 x 3 days. Twenty patients with ovarian cancer received carboplatin 350 mg/m2 and cyclophosphamide 500 mg/m2. Ten patients had cancer of unknown primary and received carboplatin 400 mg/m2, epirubicin 60 mg/m2, and etoposide 120 mg/m2 x 3 days. The OND schedule consisted of methylprednisolone 40 mg intravenous bolus followed by OND 8 mg in a 15-min infusion before chemotherapy, followed by OND 4 mg orally x 3 on the same and the next 2 days. Patients who did not experience nausea and vomiting with OND continued with an MCP schedule consisting of methylprednisolone 40 mg bolus followed by MCP 2 mg/kg in a 15-min infusion before chemotherapy, followed by MCP (20 mg x 4 on the day of therapy and the next 2 days after). Patients who failed with MCP or OND continued with OND. Considering our results as a whole, the intensity of nausea does not appear to influence the results of Gralla's scale. The results of Gralla's scale do not appear to be affected by the analysis of the antiemetic results and nausea on the next 2 days following chemotherapy administration. Overall, patients received 145 cycles with OND and 159 cycles with MCP. Of the 76 patients receiving OND-based antiemetic regimen during the first cycle, 13 (21%) experienced severe vomiting (Grade 2, 3) and the remaining 63 (79%) had mild or no vomiting (Grade 0, 1). Patients with Grade 0, 1 vomiting (63, 83%) continued with MCP in the second cycle. The final number of patients who failed on MCP, after 4 cycles of chemotherapy increased to 33 (43%); 43 (57%) were able to complete chemotherapy with MCP. Headache occurred in 15 (10%) cycles with OND and 8 (5%) with MCP. Flushing was noted in 12 (8%), and constipation occurred in 43 (30%) of OND cycles, and extrapyramidal manifestations occurred in 3 (5%) of patients receiving MCP. Diarrhea was noted in 3 (2%) of cycles with OND and in 28 (18%) with MCP. The cost ratio between MCP and OND was 1:14. If we administered OND only in patients who needed it, the overall cost decreased to 44%. Following the strategy applied in the present study, the cost decreased to 47%.

Preliminary evaluation of the potential prognostic value of serum levels of immunoglobulins (IgA, IgM, IgG, IgE) in patients with gastric cancer.

Sixty patients with advanced gastric carcinoma who refused to receive cytotoxic chemotherapy were examined for serum immunoglobulin levels (IgG, IgM, IgA, IgE). Three samples were obtained every two months thereafter. The group of patients who had above-normal values of one or more of the examined immunoglobulins had a longer survival than the other (p < 0.024). Immunoglobulin values were independent of the Helicobacter pylori antibody titer and of acute phase reactants. It is concluded that survival potentially correlates with serum immunoglobulin levels. Further studies including larger numbers of patients and correlating serum immunoglobulin levels with specific clinical parameters are needed to establish the prognostic role of serum immunoglobulins in patients with gastric carcinoma.

Unusual development of an abdominal neoplasm in a patient with Maffucci's syndrome.

A case of Maffucci's syndrome complicated by a mixed abdominal tumor with ascites in a 23-year-old female patient is described. As far as we know, this is the first such case in the literature.

Pyomyositis.

A case of non-tropical pyomyositis (PM), in a 63-year-old female patient, affecting gluteus and intrapelvic muscles is presented. Delayed diagnosis and treatment led to long-standing morbidity. Magnetic resonance imaging (MRI) of the pelvis provided valuable information on the nature and extent of the disease and helped to plan surgical management. MRI of the pelvis should be undertaken at an early-stage. Prompt examination of material obtained by aspiration or debridement would then permit an accurate diagnosis and appropriate management.

Efficacy of ondansentron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study.

The aim of the present randomized study was to evaluate which dose of Ondansentron (OND)(32 versus 8 mg) is appropriate for the antiemetic treatment of a uniform group of patients (pts) with Non Small Cell Lung Cancer (NSCLC) who were treated with Cisplatin (CDDP) 100 mg/m2 in combination with other less emetogenic drugs. One hundred and ten patients, with histologically confirmed NSCLC entered this randomized study. They were between 50 - 70 years old, with no previous Chemotherapy, with a PS (Karnofsky) >60%. They were randomized into two groups; Group A: OND as a 32 mg dose the first 24 hours, followed by 8 mg every 8 hrs for the following four days, combined with dexamethasone, 8 mg i.v. the first day, and 8 mg p.o., in the morning, the following three days. Group B: OND as a 8 mg dose every day for 4 days, combined with dexamethasone 8 mg i.v. and 8 mg p.o. the following three days. In this randomized study, of the 110 patients who entered, 106 were evaluable. Clinical parameters were similar between the examined groups. A higher number of patients of Group A presented complete response (P 0.0001), compared to patients of Group B who failed (P 0.004), during the first 24 hours. In the 3 days that followed, a higher number of pts of Group A presented complete response to the antiemetic therapy (P 0.001, P 0.0001), while Group B failed (P 0.007, P 0.001, P 0.019), or presented minor response (P 0.0001, P 0.004). Patients who had no antiemetic response needed additional therapy and were excluded from the evaluatio (13 pts of Group B). Retches (P 0.0001, P 0.005), and nausea (P 0.0001, P were also frequent in Group B. We concluded that reduced OND doses (8 mg) are inadequate in the prevention of emesis after high dose CDDP (100 mg/m2) and should be avoided.

Comparative study of tropisetron with the addition of dexamethasone or alprazolam in breast cancer patients receiving adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin and 5-fluorouracil).

We studied tropisetron (T) in patients with breast cancer receiving standard adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin and 5-fluorouracil) over 3 consecutive cycles; T was administered alone or in combination with dexamethasone (D) or alprazolam (A). 50 women entered and during the 1st cycle patients received T i.v. before chemotherapy and the same dose orally on each of the following 3 days. In the 2nd cycle, T was administered together with D and during the 3rd cycle, T was combined with A and continued with T over the ensuing 3 days post-chemotherapy. Stress was present in 23 women and was evaluated for its impact on antiemetic response. Differences in the emetogenic response were found for nausea and vomiting mainly with the addition of A. The combination of T+A was superior to T and T+D in acute emesis (P<0.001). Concerning delayed emesis, differences were detected with both T+D and T+A (being equally effective) and superior to T alone (P<0.001). The emetogenic potential was decreased by the addition of A in comparison to T alone (P=0.001). Patients without stress had no difference, while patients with stress had a significantly better antiemetic result with the addition of D or A to T. In conclusion, T provides a satisfactory result in controlling nausea and emesis caused by moderately emetogenic CT regimens. Addition of D or A improves the antiemetic effect, and A provides better coverage in women with stress, a finding worth exploration in larger confirmatory studies.

Metastatic renal clear cell carcinoma mimicking stage IV lung cancer.

We present a 63-year-old man who was investigated for a lesion in the apex of the left lung and a coexisting osteolytic lesion in the right major trochanter. FNA of the thoracic mass was suggestive for malignancy yet not diagnostic regarding the tumor type and the site of the primary tumor. A diagnosis of a stage IV lung cancer was favored and he underwent a left exploratory thoracotomy in view to resect the primary tumor. An extrapulmonary mass localized to the pleura not involving the ipsilateral lung was disclosed. Multiple biopsies revealed metastatic clear cell RCC. A 5 x 7 cm left renal tumor was revealed in a postoperative abdominal CT scan. He was treated with combination of interferon A and vinblastin followed by radical nephrectomy. Twenty-four months after the diagnosis he is alive without evidence of local or distant recurrence. Pleural metastases from RCC are mainly presented as malignant pleural effusions. Thoracic metastatic lesions localized to the pleura, forming solitary or multiple mass(es) have been rarely reported. We review the literature regarding this rare clinical manifestation of the disease and we discuss diagnostic and therapeutic options.

A case of systemic karyomegaly associated with interstitial nephritis.

A case of systemic karyomegaly is described for the first time in Greece. This rare disease entity was first described in 1979 by Mihatsh and so far only nine cases have been reported. Typical clinical features are progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Typical histologic findings are markedly enlarged and hyperchromic nuclei in tubular cells of the nephron and interstitial fibrosis surrounding the atrophic tubules.

A recently recognized entity associated with the treatment of acute promyelocytic leukemia: the retinoic acid syndrome.

All-trans-retinoic acid is an effective induction treatment for acute promyelocytic leukemia. Although retinoic acid is well tolerated by the majority of patients with this disease, a potentially fatal complication of this kind of treatment has been reported: "the retinoic acid syndrome". We describe this syndrome, which occurred in one of our patients and was successfully treated by the administration of dexamethasone.

Hepatocellular carcinoma presenting with paraneoplastic neurologic syndrome in a hepatitis B surface antigen-positive patient.

We report a hepatitis B surface antigen-positive patient who presented with paraneoplastic peripheral sensorimotor polyneuropathy and cranial nerve involvement, 6 months before a diagnosis of hepatocellular carcinoma was made. This makes us think that neurologic manifestations in hepatitis B surface antigen-positive patients warrant investigation to exclude an underlying hepatocellular carcinoma.

Experimental renal papillary necrosis. Effects of beta adrenergic receptor blockade, heparin and hydrocortisone.

Renal papillary necrosis was induced in rats by daily subcutaneous injection of 15 mg 2-bromoethylamine hydrobromide (BEA) per 100 g of body weight for 2 successive days. This dose was 50% higher than that reported previously. Beta adrenergic receptor blockade with oxyprenolol did not influence the kidney damage. The administration of heparin did not show any effect. The doses applied did not induce the incoagulability for a sufficient period of time. On the contrary, treatment with hydrocortisone decreased papillary necrosis without inducing increased diuresis.

Subclinical multisystemic autoimmunity presenting as a progressive myelopathy.

Autoimmunity can manifest clinically in many ways; however, despite the various efforts to classify autoimmune disorders into specific disease entities, the borders between these disorders remain, in many cases, unclear. In this report we describe a young woman with subclinical Sjögren's syndrome and biliary cirrhosis, who presents clinically with symptoms exclusively from the central nervous system. This neurological syndrome is consistent with a progressive myelopathy. Although the patient has a serologically and histologically confirmed multisystemic autoimmune disorder, she fulfills none of the classification criteria for the diagnosis of a specific connective tissue disease.

Ondansentron and dexamethasone treatment with different dosing schedules (24 versus 32 mg) in patients with non-small-cell lung cancer under cisplatin-based chemotherapy: a randomized study.

The purpose of this study was to determine whether ondansentron given to patients with non-small-cell lung cancer (NSCLC) undergoing cisplatin-based chemotherapy, has better antiemetic activity administered every 6 or 8 h in controlling cisplatin-induced emesis. All patients had previously received 3 cycles of cisplatin-based chemotherapy at a dose of 100 mg/m(2). Ondansentron was given according to two schedules in group A (50 patients) at a dose of 8 mg in 100 ml normal saline over 10 min i.v. infusion, together with dexamethasone 8 mg before the infusion of cisplatin, continued with both drugs at the same dose and administration after 8 and 16 h; in group B (50 patients) both drugs were administered before the infusion of cisplatin, continued after 6, 12 and 18 h. During the next 3 days, patients continued with tablets of dexamethasone 4 mg and ondansentron 8 mg, group A every 8 h, and group B every 6 h. The only difference in terms of antiemetic response that was noticed between the two groups was the number of patients experiencing nausea which was found increased in group A (n = 32) in comparison to group B (n = 25) (p < 0.022). No difference was noticed in the number of vomiting episodes and retches or emesis control, during the 3-day evaluation period after cisplatin infusion or in side effects. In conclusion, the total dose of 24 mg ondansentron during the acute phase of emesis is as effective as the total dose of 32 mg.