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.].

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.

Purpose: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non-small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen.Patients and Methods: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m(2)) and gemcitabine (1,000 mg/m(2)) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks.Results: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m(2) in pretreated patients, whereas it continued to 150 mg/m(2) in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m(2) was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombacytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival war 70%.Conclusion: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way. (C) 1999 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.

The efficacy of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) in the management of infectious exacerbations of chronic bronchitis was evaluated in a double-blind, placebo-controlled study in parallel groups over 5 months (60 days of treatment and 90 days of follow-up). The study enrolled 580 patients, of whom 514 could be evaluated. The pidotimod group had fewer and shorter infectious episodes, fewer days of antibiotic therapy and fewer days unable to undertake normal activities. The difference vs. placebo was significant during the follow-up period and, in those subjects with a less severe history, during the treatment period also. Pidotimod was well tolerated.

The aim of the investigation was to study directly the IL-2 receptor (IL-2 R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients’ PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35–79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2 R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2 R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2 Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2 R, there is a normal release of soluble IL-2 R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2 R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.

The aims of the investigation were 1) to determine if there are defects in interleukin-2 (IL-2) regulation on either phytohemagglutinin (PHA)-activated or non-PHA-activated peripheral blood mononuclear cells (PBMC) in cancer patients to ascertain the role of IL-2 in this disease; 2) to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL-2 production by PBMC cultures; and 3) to evaluate the IL-2 receptor expression by PBMC of cancer patients. An assessment of lymphocyte subsets was also performed with monoclonal antibodies in a selected group of patients. A total of 170 patients entered the study. Cancer sites were larynx (48), breast (44), lung (30), colorectal(23), and gynecologic (25). Staging showed in the former three cancer sites predominantly localized or only locally advanced disease and in the latter two sites disseminated disease. PBMC cultures were performed with microtiter plate technique and 3H-thymidine uptake evaluation using polyclonal mitogens, IL-2, and a monoclonal antibody against IL-2 receptor. Our results provided evidence that the cancer patients exhibit a T-cell functional immunodepression, which, to some extent, progresses during tumor growth so that the localized disease shows a low-grade defect and advanced disease a high-grade defect. Our data also clearly suggest that IL-2 deficiency is the primary factor involved in this functional immune impairment. We found no significant defect in the IL-2 receptor expression by PBMC of cancer patients. Our data also seem to support the in vivo therapeutic administration of IL-2 and lymphokine-activated killer cells to cancer patients.

The aims of the investigation were: 1) to determine if there are defects in interleukin 2 (IL 2) regulation either on phytohemagluttinin (PHA)-activated or non PHA-activated peripheral blood mononuclear cells (PBMC) in cancer patients, in order to ascertain the role of IL 2 in this disease, and 2) to carry out preliminary experiments for a direct quantitative evaluation of endogenous IL 2 production by PBMC cultures of cancer patients. An assessment of lymphocytes subsets was also performed with monoclonal antibodies in a selected group of patients. A total of 159 patients entered the study. Cancer sites were: larynx, 49; breast, 42; lung (NSC), 25; colorectal, 18; and gynecologic, 25. In the former 3 cancer sites, staging showed localized or only locally advanced disease and in the later 2 sites it showed disseminated disease. Our results provided evidence that the cancer patients exhibit a T cell functional immunodepression, which progresses during tumor growth, so that the localized disease shows a low-grade defect and advanced disease shows a high-grade defect. Our data also clearly suggested that the factor involved with a primary role in this functional immune impairment is the IL 2 deficiency. In our study we have not found a substantial difference of activity between recombinant and nonrecombinant IL 2, although the comparison of the relative activities of the two types of IL 2 is not easy to make, since they are expressed in different ways; however the recombinant one appeared to be slightly more active, probably for the higher purity. Our data also seem to support the perspective of the in vivo therapeutic administration of IL 2 in cancer patients.