Use of combination CT (HAI+ SYS) in liver metastases from CRC: a randomized trial from giscad-sitilo/G. Pancera, G. Luporini, FM Fiorentini, S. Tumolo, S. Cortesi, S. Barni, C. Ceravolo, P. Comella, B. Massidda, F. Cirillo, B. Andreoni, F. Montinari, R. Labianca.-In: ANNALS OF ONCOLOGY.-ISSN 0923-7534.-11: suppl. 2 (2000), pp. 72-72.((Intervento presentato al 2. convegno National Congress of Medical Oncology tenutosi a Genova nel 2000.

Aims and background: To evaluate the rate of cancer patients who do not fill out a quality of life (QL) questionnaire, their characteristics and the reasons for not filling out the QL questionnaire.Methods: Consecutive cancer patients who were seen in 79 Italian medical oncology and radiotherapy centers over a period of one week were asked to fill out a questionnaire concerning the importance of 46 domains of quality of life, each one scored on 4 levels (not at all, a little, much, and very much).Results: Of 6,918 cancer patients, 820 (11.9%) did not fill out the questionnaire. The most important reasons for not complying were: illiteracy (17.9%), lack of glasses or poor eye-sight (17.4%), poor physical condition (11.9%), poor psychological condition (5.9%), refusal (28.7%). The questionnaires significantly less filled out were those of older patients with low performance status and educational level or with locally advanced or disseminated disease and inpatients.Conclusions: The results of the study reveal the risk of selection bias in QL assessment in randomized controlled trials and suggest the need for more complete information regarding the aim of QL evaluation and the necessity of a proxy's help to overcome the problem, with the awareness that the proxy's influence could modify the response. The impact of the lack of patient compliance on the QL results still remains to be evaluated.

Background: Studies are available showing that cancer patients in southern Europe may be less well informed about their disease than patients in northern Europe and North America.Patients and methods: In the framework of a survey aimed at exploring the meaning of quality of life for the Italian cancer patient, carried out all over Italy in a one-week time span on 6098 consecutive patients, two visual analogue scales evaluating severity and curability of disease were also submitted to the patients. Four patterns of patients' answers were defined: very easy/difficult-to-cure disease, and not-severe/severe disease. Multifactorial analyses were performed using logistic models for each of the four responses, assuming patient characteristics, time since diagnosis and disease extent as explanatory variables.Results: Only 26% of 2088 patients with disseminated disease believed it to be 'difficult to cure', while 39% felt it to be 'easy to cure'. In the same subgroup of patients, only 47% found their disease `severe'.Conclusions: Authors were impressed by these unexpected results, which are therefore reported separately from the overall analysis of data, aimed at exploring the quality of life domains for the Italian cancer patient. In fact, they would suggest a great lack of awareness of the severity and curability of their disease in a large group of unselected Italian cancer patients. This may depend on various factors, including cross-cultural ones, but could also be partly related to inadequacies in the process by which the Italian patient is informed, and this should be further investigated.

Granisetron has been shown to exert a beneficial therapeutic effect in the prophylaxis and treatment of acute nausea and vomiting clue to chemotherapy. However, limited data regarding its efficacy in the prevention and treatment of delayed emesis are available. A total of 532 patients entered this multicenter double-blind study, aimed at comparing the efficacy and safety of intramuscular (i.m.) granisetron with that of i.m. granisetron plus dexamethasone. Complete response and total control were evaluated for 3 days following the first 24 h after cisplatin administration in two groups of patients: 262 treated with granisetron 3 mg i.m. daily (plus placebo), and 265 with granisetron at the same dose plus dexamethasone 8 and 4 mg twice daily. The rate of complete response was 58.0% in the granisetron group and 78.9% in the granisetron plus dexamethasone group over days 1-3 (p<0.01). Similarly, over the same period total control was 44.7% with granisetron alone and 65.3% with granisetron plus dexamethasone (p<0.01). Local and systemic tolerability of the i.m. therapy with granisetron were satisfactory. In conclusion, granisetron plus dexamethasone showed good protection against delayed emesis due to emetogenic chemotherapy. [(C) 1999 Lippincott Williams & Wilkins.].

Purpose: A 5-hydroxytryptamine 3 (5-HT3) receptor antagonist plus dexamethasone is the most efficacious antiemetic prophylactic treatment for the prevention of cisplatin-induced acute emesis, but the optimal intravenous (IV) dose of dexamethasone is unknown. This prompted us to perform a multicenter, randomized, double-blind, dose-finding study that compared four different doses of dexamethasone.Patients and Methods: Patients were randomized to receive dexamethasone, either 4, 8, 12, or 20 mg, administered by 15-minute IV infusion 45 minutes before cisplatin. Ondansetron 8 mg was added to dexamethasone and was administered IV 30 minutes before cisplatin. From March 1996 to July 1997, 531 patients were enrolled onto the study and 530 were assessable according to the intention-to-treat principle (133 patients received 4 mg; 136 patients, 8 mg; 130 patients, 12 mg; and 131 patients, 20 mg of dexamethasone).Results: Complete protection from acute vomiting and nausea was achieved by 69.2% and 60.9% of patients, respectively, who received 4 mg of dexamethasone, by 69.1% and 61.0% of those who received 8 mg, by 78.5% and 66.9% of those who received 12 mg, and by 83.2% and 71.0% of those who received 20 mg of dexamethasone. Complete protection from vomiting was significantly superior in patients who received 20 mg compared with those who received 4 and 8 mg of dexamethasone (P < .005) and was superior, but not significantly, compared with those who received 12 mg. Complete protection from nausea was superior, but not significantly, in patients who received 20 mg of dexamethasone. Multifactorial analysis confirmed these results. Antiemetic treatment was well tolerated, and no significant difference was found among the four groups in the incidence of adverse events.Conclusion: A 20-mg single IV dose of dexamethasone should be considered the most efficacious prophylactic dose for the prevention of cisplatin-induced acute emesis. J Clin Oncol 16:2937-2942. (C) 1998 by American Society of Clinical Oncology.

From December 1992 to July 1994, 973 consecutive patients scheduled to receive for the first time cisplatin at doses ≥ 50 mg/m2, used alone or in combination with other antineoplastic agents, entered a doubleblind multicenter randomized study comparing ondansetron (OND) 8 mg iv vs granisetron (GRAN) 3 mg iv, both diluted in 50 ml normal saline and administered in 15 minutes, 30 minutes before chemotherapy. Dexamethasone (DEX) 20 mg iv was added to the 5-HT3 antagonists and administered in 15 min, 45 min befure chemotherapy. Nine hundred and sixty-six patients (483 receiving OND and 483 GRAN) were evaluable for intention to treat analysis. Patient characteristics were well balanced between the two antiemetic treatments. Complete protection from acute vomiting/nausea was obtained in 383 (79.3%)/348 (72.1%) of patients receiving OND and in 386 (79.9%)/347 (71.8%) of those receiving GRAN. During day 2–4 after chemotherapy patients received the same antiemetic prophylaxis for delayed emesis (metoclopramide 20 mg 4 times/day + DEX 8 mg im × 2 on day 2–3 and 4 mg im × 2 on day 4). Complete protection on day 2–6 from vomiting/nausea was obtained in 69.7%/52.9% and 70.0%/49.6%, respectively. Adverse events were mild and not significantly different between the two antiemetic regimens. In conclusion, OND 8 mg and GRAN 3 mg, both combined with DEX, showed similar efficacy and tolerability in the prevention of acute and delayed cisplatin-induced emesis; therefure, the choice between them should be made on the basis of acquisition costs. Supported by AUCC (Associazione Umbra Contro il Cancro). From December 1992 to July 1994, 973 consecutive patients scheduled to receive for the first time cisplatin at doses ≥ 50 mg/m2, used alone or in combination with other antineoplastic agents, entered a doubleblind multicenter randomized study comparing ondansetron (OND) 8 mg iv vs granisetron (GRAN) 3 mg iv, both diluted in 50 ml normal saline and administered in 15 minutes, 30 minutes before chemotherapy. Dexamethasone (DEX) 20 mg iv was added to the 5-HT3 antagonists and administered in 15 min, 45 min befure chemotherapy. Nine hundred and sixty-six patients (483 receiving OND and 483 GRAN) were evaluable for intention to treat analysis. Patient characteristics were well balanced between the two antiemetic treatments. Complete protection from acute vomiting/nausea was obtained in 383 (79.3%)/348 (72.1%) of patients receiving OND and in 386 (79.9%)/347 (71.8%) of those receiving GRAN. During day 2–4 after chemotherapy patients received the same antiemetic prophylaxis for delayed emesis (metoclopramide 20 mg 4 times/day + DEX 8 mg im × 2 on day 2–3 and 4 mg im × 2 on day 4). Complete protection on day 2–6 from vomiting/nausea was obtained in 69.7%/52.9% and 70.0%/49.6%, respectively. Adverse events were mild and not significantly different between the two antiemetic regimens. In conclusion, OND 8 mg and GRAN 3 mg, both combined with DEX, showed similar efficacy and tolerability in the prevention of acute and delayed cisplatin-induced emesis; therefure, the choice between them should be made on the basis of acquisition costs. Supported by AUCC (Associazione Umbra Contro il Cancro).

Background: Differences in pharmacodynamic and pharma- cokinetic characteristics among serotonin-receptor antagonists have been reported in preclinical studies. This prompted us to carry out a study to determine whether such differences are important in terms of clinical efficacy or tolerability.Patients and methods: 973 consecutive cancer patients scheduled to receive cisplatin for the first time (at doses greater than or equal to 50 mg(2)), entered a double-blind multicenter randomized study comparing intravenous ondansetron 8 mg versus granisetron 3 mg. Dexamethasone 20 mg was added to both serotonin antagonists. On days 2 to 4 after chemotherapy all patients received oral metoclopramide plus intramuscular dexamethasone as antiemetic prophylaxis for delayed emesis. Nausea and vomiting were assessed daily until day 6 after chemotherapy.Results: We evaluated 966 patients (483 receiving ondansetron and 483 granisetron). Complete protection from acute vomiting/nausea was obtained in 79.3%/72.0% of patients receiving ondansetron and in 79.9%/71.8% of those receiving granisetron. Complete protection from delayed vomiting/nausea was obtained in 69.7%/52.9% and 70.0%/49.6% of patients receiving the ondansetron or granisetron regimens, respectively. Adverse effects were mild and not significantly different between the two antiemetic regimens.Conclusions: Ondansetron 8 mg and granisetron 3 mg, both combined with dexamethasone, showed similar efficacy and tolerability in the prevention of cisplatin-induced emesis. The choice between the two regimens can be dictated by their respective purchase prices.

Sixty patients with advanced colorectal cancer were randomized between cisplatin (60 mg/mq i.v. every 3 weeks) + 5-fluorouracil (600 mg/mq i.v. bolus/weekly) and 5-fluorouracil alone (same schedule). In the 54 evaluable patients, no CR was observed. PR rate was 19.2% for the combination, and 14.5% for the monochemotherapy. Also the overall median survival time was similar for the two arms (10 and 13 months, respectively). Toxicity was acceptable, with more side-effects in the combination arm. Both treatments are of limited activity in advanced colorectal cancer and no advantage comes out from the use of this polychemotherapy.

The survival and the remission length of a group of 122 adult patients with lymphomas have been studied: 45 Hodgkin (HG) and 77 non-Hodgkin lymphomas (NHG). The difference between the survival medians of the two groups turned out statistically significant (74.5 for HG cases and 43 for NHG). Non significant survival differences were detected among HG with "favourable" and those with "non-favourable" histology. Determinant for the survival was the obtention of the complete remission both in HG and in NHG. As far as the treatment is concerned in relation to the stage, HG were broken down into three groups: radiotherapy alone, chemo + radiotherapy, chemotherapy only. The highest percentage of complete remissions (RC) was obtained in the group chemo + radiotherapy (100% of the treated) versus 80% on the group with the only radiotherapy and 53.3% of that with the only chemotherapy. The median length of the RC was, however, higher in the patients treated with chemotherapy alone. After relapse a new RC easily obtained with chemotherapeutic treatment in the patients treated with only radiotherapy in comparison with those already submitted to chemotherapy. As far as NHG is concerned, they were broken down according to the main histotype in lymphocytic and histiocytic. The groups, according to the treatment turned out two: radiotherapy plus chemotherapy and chemotherapy alone. The difference between the survival medians turned out highly statistically significant (43 and 36 cases respectively). Also statistically significant, but in favor of th histiocytic cases, the percentage of the patients who maintained the CR (27 cases the lymphocytic versus 60 for the histiocytic) this in agreement with the literature data, according to which, even being the histotypes with the most unfavourable prognosis, the histiocytic, once attained the CR, tend to maintain the same, more longer in time, in comparison with the forms with favourable histology. The chemotherapeutic combinations employed by us are subsequently outlined extensively.

The Authors report the preliminary results of a two-step far-reaching investigation carried out on cancer patients to study: 1) the immune conditions of the patients and establish, by a thorough immune monitoring, employing tests of humoral immunity (tetanus toxoid response), of delayed immunity (BCG test, PHA-lymphocyte blastogenesis, MIF release, skin window) and macrophage immunity (skin window), the chemotherapy effects on the immune conditions and the most suitable time to carry out immunotherapy; 2) the immunotherapeutic results which can be obtained with three different immunogens (BCG, C. parvum and ribonucleotides). The results obtained in the first part of the investigations pointed out the usefulness of the tests adopted to follow up the evolution of the immunological reactivity in patients submitted to chemotherapy, while the results of the immunotherapeutic trial show a preliminary character and, at present, do not allow definitive conclusions. Carefully planned and randomized studies are at present under way to establish, more thoroughly, the optimal modalities and the real possibilities of the immunotherapy performed with C. parvum and ribonucleotides in cancer patients.