The anti-emetic efficacy of tropisetron plus dexamethasone in patients treated with high-dose chemotherapy and stem cell transplantation.

Among the most distressing symptoms experienced by patients who have undergone high-dose chemotherapy and stem cell transplantation are nausea and vomiting. The chemotherapy regimens used in high-dose conditioning protocols are highly emetogenic. The 5HT3 receptor antagonists are very effective in the prevention and abolition of nausea and vomiting resulting from chemotherapeutic drugs. One of them, tropisetron, is a selective antagonist of serotonin 5HT3 receptors with proven efficacy against emesis. Dexamethasone is also known as an effective agent against nausea and vomiting. The addition of dexamethasone to a 5HT3 receptor antagonist is synergistic, as has been shown in many trials with highly emetogenic drugs. The aim of the present trial was to study the efficacy and safety profile of the combination of tropisetron and dexamethasone in controlling nausea and vomiting in patients receiving megatherapy prior to stem cell transplantation. We studied 31 patients. All of them were evaluable for response and toxicity. The majority of patients achieved complete or major protection against acute vomiting (71-83%), and 67-84% of the patients had no or mild nausea. The combination was tolerated well, and only a minority of patients reported side effects. Among them the most common were headache (in three patients) and constipation. No patient withdrew from the study because of toxicity. It has become evident from our data that the administration of 5 mg tropisetron daily in combination with 20 mg dexamethasone for 8 days can prevent the acute emesis otherwise experienced by patients receiving high-dose chemotherapy as conditioning in stem cell transplantation programmes.

Predictive factors affecting mobilization and peripheral blood stem cell (PBSC) collection using single apheresis (SA) for rescuing patients after high-dose chemotherapy (HD.CHE) in various malignancies.

We have investigated factors that affect the efficiency of single apheresis (SA) before transplant and define groups of patients that may require more than one collection for hematologic support. A consecutive series of 56 patients with hematologic malignancies and solid tumours had peripheral blood stem cells (PBSC) collected following mobilization with colony-stimulating factors (CSF) alone or after conventional chemotherapy (CHE) or high-dose cytoxan (HD.CY) followed by CSF. The efficiency of SA was assessed by total mononuclear cell number (MNC) in the harvest, CD34+ cells and colony-forming units (CFU). Linear regression analysis was performed to determine factors that affect SA yield as assessed by the above parameters. Thirty-five patients were mobilized once, 13 patients twice, six patients required three, one required four and one required five aphereses. Suboptimal mobilization and collection by SA occurred in patients with extended previous radiotherapy (RT) and patients older than 50 years. The number of CHE cycles given in the past also had an adverse effect on SA efficiency. In contrast, disease status, bone marrow infiltration by malignant cells, type of CHE, time since last CHE and mobilization regimen used were not significantly related to the collection efficiency by SA. Age, extent of previous RT and amount of CHE given prior to mobilization define the patients who require more than one SA course for support regardless of the underlying disease, BM status or mobilization regimen used. In such patients a plan for multiple aphereses should be scheduled in advance.

Peripheral blood progenitor cell (PBPC) transplantation with a single apheresis in patients with lymphoma, myeloma and solid tumors.

The aim of this study was to investigate if a single apheresis after peripheral blood progenitor cell (PBPC) mobilization can be used to rescue patients receiving high dose chemotherapy (HD.CHE) as treatment for an underlying malignancy. Eighteen consecutive patients who were admitted to the transplant unit for treatment were leukapheresed following mobilization with one of the following protocols: group I: rHuG-CSF alone, group II: conventional chemotherapy (C.CHE) + rHuG-CSF or rHuGM-CSF and group III: high dose cytoxan (HD.CTX) + rHuG-CSF. The optimal day for leukapheresis was determined by following white blood cell counts (WBC), mononuclear cell counts (MNC) and CD34+ cell counts daily. Granulocyte-macrophage colony-forming cells (GM-CFC) assay was performed at the leukapheresis product and prior to reinfusion. All patients proceeded directly to ablative therapy according to their underlying malignancy. PBPC from single apheresis were reinfused to all patients and cytokines started 24 h after infusion. Hematologic recovery after HD.CHE was the parameter used to ensure successful engraftment. We have been able to recover adequate number of PBPC for transplantation with a single apheresis in all patients. The number of infused cells were for groups I, II and III: (1) median number of MNC 4.7, 3.58 and 2.79 x 10(8)/kg, respectively (2); median number of CD34+ cells 4.4, 2.8, 2.7 x 10(6)/kg, respectively. The median apheresis day was 6, 16 and 16, respectively. Recovery times to granulocyte count > 0.5 x 10(9)/ L was 9 d (range 9-12) and to platelets > 20 x 10(9)/L was 12 d (range 1-135); 17/18 patients have engrafted successfully independent of the mobilization method used. These data suggest that sufficient PBPC can be harvested at a single leukapheresis for hemopoietic rescue after myeloablative therapy. Rapid hematologic recovery occurs when cytokines alone after conventional or HD.CHE are used for mobilization. Results of collection products and hematopoietic recovery are independent of the mobilization technique used.

A phase II study of ondansetron as antiemetic prophylaxis in patients receiving high-dose polychemotherapy and stem cell transplantation.

The field of high-dose chemotherapy with stem cell transplantation has been expanded recently as a treatment for solid tumors and hematological malignancies. Severe emesis remains one of the main extramedullary side-effects of high-dose regimens during the first week of treatment. Traditional antiemetics such as chlorpromazine, diazepam, and phenothiazines are extensively used but are unable to control emesis. The new antiemetic ondansetron, a serotonin receptor (5HT3) antagonist appears to be superior to these drugs for cisplatin-induced emesis. The study we present here is an attempt to control emesis following high-dose regimens, during bone marrow or peripheral stem cell transplantation, with ondansetron. To our knowledge no other paper has reported the efficacy of this antiemetic in such group of patients. A total of 29 patients who received highly emetogenic polychemotherapy as conditioning regimens for bone marrow transplantation were treated with ondansetron, which was given as an 8-mg i.v. short infusion prior the initiation of treatment and every 6 h thereafter for 3 days, and an 8-mg dose every 8 h for 5 additional days. All the patients had previously been treated with chemotherapy and were evaluable for response and toxicity. Complete and major protection of vomiting on day 1 was achieved by 76% of the patients, 58% on day 2 and 52% on day 3. Nausea was absent or mild in 79% of patients on day 1, 45% on day 2 and 41% on day 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Combination chemotherapy with cis-platinum, adriamycin, mitomycin-C (PAM) in patients with advanced bladder cancer.

Thirty patients with advanced bladder cancer received combination chemotherapy with cis-platinum, adriamycin and mitomycin C. Two patients (6.6%) responded completely and survived 24 and 30 months. Partial response was noted in 14 patients (46.6%) who had a median survival of 9.6 months. Eight patients (26.6%) had stable disease with a median survival of 5 months whereas in 6 patients (20%) their disease progressed with a median survival of 3 months. The amelioration of hematuria, regardless of response, was impressive. Nausea and vomiting were the commonest side effects. Myelotoxicity was mild and reversible. We conclude that PAM chemotherapy is effective and well tolerated in patients with advanced bladder cancer.