Spiritual well-being of Italian advanced cancer patients in the home palliative care setting.

This study evaluates the spiritual well-being (SpWB) in very advanced cancer patients assisted by the home palliative care program of ANT Foundation, a no-profit Italian organisation. SpWB was assessed by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp12), including Meaning, Peace, and Faith subscales. The quality-of-life (QoL) was evaluated by using the Functional Assessment of Cancer Therapy-General scale. Questionnaires were distributed to 1,055 patients and 683 were compiled and evaluable for analysis. The mean scores of FACIT-Sp12 as well as of QoL were notably lower than reference values for cancer survivors. The FACIT-Sp12 score was higher in patients with less impaired Karnofsky Performance Status, fully participating in religious rituals and living in central Italy. A high Pearson's correlation was found between QoL and FACIT-Sp12 (r = .60), Peace (r = .71) and Meaning (r = .52), while it was marginal for Faith (r = .27). The hierarchical regression analysis showed that FACIT-Sp12 is a significant predictor of QoL. The study suggests that Italian patients with advanced cancer assisted by expert multi-professional teams in the home palliative care setting have a low level of SpWB thereby highlighting the need for the integration of spiritual support as part of comprehensive cancer care.

New challenges and old problems: end of life care and the dilemma of prognostic accuracy.

Dignity of the natural end of life for everybody is one of the new great challenges of medicine and social care for the beginning 21st century. However, many end of life care providing doctors are confused about how to categorize the help they give. One of the central problems is predicting the life expectancy of an individual patient. Difficulties in this field can become ethical dilemmas when physicians are obliged to predict accurately a patient's prognosis as the basis for a certain care strategy. Clinical estimation of the duration of life for patients with end of life cancer needs experience and training. Education programmes in the field should include this topic much more until now. Prognosis should be based more on proven indices and less on intuition. However, there is no doubt that daily clinical practice limits the use of highly sophisticated computer-based score models. Even maximal accuracy of prognosis will not exclude the risk of errors in a great part of patients. This limits their classification in care categories too strictly defined. Health care systems should avoid models for care with standards and budgets based on prognostic estimates and the medical community should avoid claim by disciplines of certain categories of patients defined by their prognoses. What we need is a network of assistance for incurable patients with single parts defined by patients needs and not by predicted life expectancy. Separating palliative and terminal care is artificial and often in contrast to the needs of the patients.

Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study.

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.

Phase II study of sequential treatment of advanced non-small-cell lung cancer: three cycles of high-dose epirubicin plus cisplatin followed by weekly vinorelbine.

Previous phase I, II, and III studies on high-dose epirubicin (HDEPI), alone or in combination with cisplatin (CP), indicate an interesting activity of this drug in the treatment of non-small-cell lung cancer (NSCLC). However, the toxicological profile of HDEPI limits its prolonged use. In our experience, vinorelbine (VNR) seems to be a suitable drug for long-term monotherapy for advanced NSCLC. On these grounds, advanced NSCLC patients were treated with the following strategy: 3 consecutive cycles of CP 60 mg/m2 and HDEPI 120 mg/m2 on day 1, every 3 weeks; then, irrespective of response, weekly VNR at a dose of 25 mg/m2 was administered at home. From December 1996 to March 1998, 25 patients entered the study. After receiving 3 cycles of CP/HDEPI, 8 patients (32%) had a partial response and 3 (12%) had a minor response. Nine patients had stable disease (36%) and 4 (16%) had progressive disease. Twenty-three patients received weekly VNR, and the median number of administrations was 10 (range, 1-38). After VNR treatment, we observed a partial response in 2 patients who previously had stable disease. Therefore, the overall response rate to sequential treatment was 40%; median time to progression was 7 months (range, 2-26 months). The major toxicities due to the CP/HDEPI regimen were neutropenia (72%) and alopecia (80%). During the VNR treatment, grade 3/4 neutropenia was seen in 36% of patients. The doses and the timing of VNR administrations were modified according to toxicity. Symptoms such as cough, dyspnea, and pain, present in 21 patients before the treatment, improved in 11 cases (52%). Median overall survival is 9 months (range, 3-40+ months); one patient is still alive after 40 months. One- and 2-year survival rates are, respectively, 44% and 16%. This study confirms the activity of CP/HDEPI in NSCLC and indicates that the sequential treatment of CP/HDEPI for 3 cycles followed by weekly VNR could be considered an effective strategy for locally advanced or metastatic NSCLC.

Advanced ovarian cancer patients with no evidence of disease after platinum-based chemotherapy: retrospective analysis of the role of second-look.

From 1981 to 1992, 230 previously chemotherapy-untreated epithelial ovarian cancer patients (Stages IIb-III or IV) received platinum-based polychemotherapy at our Division. In this presentation, time to progression and overall survival rates were retrospectively analyzed in 89 epithelial ovarian cancer patients (stage IIb, c - III or IV) with no clinical evidence of disease (clinical complete remission--CCR--in 26 patients with postsurgical residual tumor > or = 2 cm, and no clinical evidence of disease--NED--in 63 patients with post-surgical residual tumor < 2 cm) after first-line platinum-containing chemotherapy. After at least 6 courses of chemotherapy, 62 patients (group A) were submitted to second-look (SL) laparotomy (n=47) or laparoscopy (n=15); 27 patients (group B) did not undergo second-look surgery because of patient refusal, the surgeon's decision or clinical contro-indications to surgery. Groups A and B were comparable in terms of post-surgical residual tumor (< 2 cm: 71% vs 70%), median Performance Status (WHO: 1) and median age (56 vs 57 yrs). FIGO stage IIb, c was more frequent in group B (26% vs 18%--p=0.004). In 9/18 (50%) patients with clinical CR and in 31/44 (70%) NED patients no residual tumor was confirmed at SL (pathological CR--pCR). After a median follow-up of 10 years (range 5-16 years), 72% (64/89) of patients relapsed and 65% (58/89) died. Survival was significantly longer in patients with pCR (median survival 76 months vs 32, 29 and 16 months for patients with pPR, pNC or pPD, respectively, p=0.0001). Multivariate analysis identifies pCR as the only significant prognostic factor exerting an influence on survival after second-look laparotomy (p=0.0000). This study confirms that the second-look can provide an important prognostic evaluation in patients without evidence of disease after chemotherapy for ovarian cancer stages III-IV.

A double-blind evaluation of the analgesic efficacy and toxicity of oral ketorolac and diclofenac in cancer pain. The TD/10 recordati Protocol Study Group.

AIM: To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain. METHODS AND STUDY DESIGN: The study was a multicenter randomized double-blind cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment. RESULTS AND CONCLUSIONS: A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (117 cross-over observations) and 257 multiple treatments (127 cross-over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly, a pronounced sequence effect was found: gastric disturbances after ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac.

Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.

PURPOSE: This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy. PATIENTS AND METHODS: Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles. RESULTS: In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups. CONCLUSION: Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.

Multicenter randomized clinical trial on high-dose epirubicin plus cis-platinum versus vinorelbine plus cis-platinum in advanced non small cell lung cancer.

BACKGROUND: High dose Epirubicin (HD-EPI) (>90 mg/m2) and Vinorelbine (VNR) demonstrated antitumor activity as single agent (about 20%) in the treatment of advanced NSCLC. This trial compares these two agents combined with cisplatin (CP). PATIENTS AND METHODS: From August 1992 to February 1996, 228 patients with locally advanced or metastatic NSCLC were randomized to receive either EPI 120 mg/m2 as i.v. bolus plus Cisplatin (CP) 60 mg/m2 on day 1 (regimen A) or VNR 25 mg/m2 as i.v. bolus on day 1 and 8 plus CP 60 mg/m2 on day 1 (regimen B). Both treatments were recycled every 21 days up to a maximum cumulative dose of EPI of 840 mg/m2 or 12 cycles. Eligible patients were 212 and 198 patients were evaluable for objective response (95 in arm A and 103 in arm B). The main characteristics of eligible patients were: male/female 179/33; median age 61 (42-72); median Karnofsky PS 80 (70-100); stage IIIA 12%, stage IIIB 40%, stage IV 41%, recurrence 7%; histotype: epidermoid 48%, adenoca 36%, others 16%. RESULTS: The following response rates were observed in regimens A and B, respectively; CR, 1 and 2%, PR, 32 and 25% (P = 0.4567). Median CR + PR duration was 9 and 8 months, respectively. Median survival was 10.5 and 9.6 months, respectively. Grade III-IV leucopenia occurred in 38 and 21% in arm A and arm B, respectively(P = 0.01), thrombocytopenia in 6 and 0% (P = 0.02), anemia in 8 and 7% (n.s.). Non-hematological toxicity was moderate and the only difference between the treatments was alopecia (88 vs. 33% in arm A and B, respectively). Supraventricular arrhythmia occurred in three patients on regimen A; a >15% LVEF absolute decrease was observed in 9 (22.5%) and three (14%) patients on arm A and arm B, respectively (n.s.). No congestive heart failure was observed. CONCLUSION: HD-EPI+CP and VNR+CP are both active combinations in advanced NSCLC with a similar response rate, response duration and survival but regimen A was significantly more toxic (myelosuppression and alopecia).

The combination of paclitaxel and carboplatin as first-line chemotherapy in patients with stage III and stage IV ovarian cancer: a phase I-II study.

The combination of paclitaxel 135 mg/m2 (24-hour infusion) and cisplatin 75 mg/m2 is now considered the standard treatment in first-line chemotherapy for stage III suboptimally debulked and stage IV ovarian cancer. Interest is focused on the possibility of evaluating the combination of paclitaxel with carboplatin, because it was found to be less nefrotoxic and less neurotoxic than cisplatin. This study seeks to determine the maximum tolerated dose and to assess the antitumor activity of the combination of a 3-hour paclitaxel infusion followed by carboplatin. Thirty-three chemotherapy-naive patients with stage III-IV epithelial ovarian cancer entered this open, nonrandomized dose-finding study. The first dose level investigated was paclitaxel 125 mg/m2 and carboplatin 250 mg/m2: the dose level progression was performed by alternatively increasing paclitaxel 25 mg/m2 and carboplatin 50 mg/m2. Cycles were repeated every 28 days. At least three patients were treated at each dose level. Overall, 233 and 224 cycles, respectively, are evaluable for nonhematologic and hematologic toxicity. Dose-limiting toxicities (febrile neutropenia and severe fatigue) were observed in two of six patients at level VIII (paclitaxel 225 mg/m2 and carboplatin 400 mg/m2) and therefore the previous dose-level (paclitaxel 200 mg/m2 and carboplatin 400 mg/m2) was considered as the maximum tolerated dose. Neutropenia (grade 3-4 in 63% of cycles), neurotoxicity (grade 2 in 37.5% and grade 3 in 9% of patients), arthromyalgias (grade 2 in 53% of patients and grade 3 in 3% of patients), and grade 3 alopecia were the most common toxicities observed. The incidence of thrombocytopenia was low (grade 3 in 4% of cycles) and no renal toxicity was observed. An objective remission was documented in 74% of 31 evaluated patients, including eight complete remissions (26%) confirmed by second-look surgery. The combination of paclitaxel 200 mg/m2 3-hour infusion followed by carboplatin 400 mg/m2 (30-minute infusion) is a safe and active regimen as first-line chemotherapy for advanced ovarian cancer.

Comparative crossover trial of two intravenous doses of granisetron (1 mg vs 3 mg) + dexamethasone in the prevention of acute cis-platinum-induced emesis.

BACKGROUND: The 5HT3 receptor antagonist Granisetron (GRA) is available on the market as a 1 mg vial in USA and as a 3 mg vial in Europe. This study aimed to compare the two i.v. doses of GRA (3 mg vs 1 mg), both of which combined with Dexamethasone (DEX) (20 mg) in the prevention of acute Cisplatinum (CP)-induced emesis. PATIENTS AND METHODS: One hundred and ninety-eight consecutive chemotherapy-naive cancer patients, mainly suffering from lung and bladder cancer, were randomized at their first cycle to receive either GRA 1 mg + DEX or GRA 3 mg + DEX as i.v. bolus prior to chemotherapy and crossed-over to another GRA dose at the second cycle. The cytotoxic treatment included different multi-drug regimens containing CP (median dose 60 mg/m2, range 50-70) administered on day 1 and repeated every 21-28 days. RESULTS: Of the 192 evaluable patients complete protection from acute emesis with GRA 1 and GRA 3, was observed after the 1st + 2nd cycles as follows: nausea 70% and 74%, vomiting 90% and 94%, nausea and vomiting 67% and 74% respectively (no statistically significant difference). No carry-over effect was observed on the complete protection from emesis. The crossover analysis comprising 156 patients confirmed there were no differences between the two antiemetic treatments. Twenty-seven per cent of patients preferred GRA 1, 31% preferred GRA 3, while 42% expressed no preference (P = 0.75). Nor was any difference observed for tolerability, the only reported side-effects being mild headache (16% vs 17%) and constipation (18% vs 25%). CONCLUSION: This study shows that, under the above conditions, the 1 mg and 3 mg i.v. GRA doses are comparably effective when combined with DEX 20 mg in the prevention of acute CP-induced emesis.

Hospital-at-Home for advanced cancer patients within the framework of the Bologna Eubiosia project: an evaluation.

AIMS AND BACKGROUND: An evaluation of the Bologna Hospital-at-Home (BHH) was undertaken to examine the following aspects: 1) median daily costs of the BHH; 2) delivery of medical services; 3) patient satisfaction with the care received and frequency of requests for transfer to the alternative setting. Delivery of services and patient's satisfaction in the BHH were compared with data collected for a traditional hospital (Ospedale Sant'Orsola Malpighi, Bologna--OSM). METHODS: Our analysis was performed as a cost analysis considering two periods of time in 1992 and 1993/94. Included were direct and indirect costs; no intangible costs were found. The patient's perspective was selected for the analysis. The observational study examining delivery of service and quality of life of patients admitted to the two care settings, BHH and OSM, considered patient's clinical history and an interview conducted by the evaluation team 6 weeks after admission to either facility. Data included patient's characteristics, quantity of diagnostic and therapeutic measures, circumstances of life, satisfaction with the care received, and intention for transfer to the alternative setting of nursing. The statistical significance of our assumption of comparable care intensity and better patient quality of life in the BHH was tested by the Pearson Chi-square test. RESULTS: A survey was carried out of 236 patients treated in the BHH or the OSM. The setting of assistance did not influence the provision of services. The time of "talking to the doctor" was notably higher for BHH than for OSM patients. The analysis of satisfaction showed that 98% of the surveyed BHH patients believed it matched the actual needs. The quality of life was considered to be reduced/bad in 67% of the OSM patients but in only 51% of BHH patients. An opinion was also requested with regard to transfer to the alternative setting of nursing: 47% of OSM patients judged BHH care would be better than traditional hospital. The median daily costs in BHH reached 118,789 Lire (range, 108,569-129,027 Lire, depending on performance status). CONCLUSIONS: Although the economic advantage of hospital-at-home care certainly is important, we would like to stress that better quality and dignity of life should be the main point supporting the idea of hospital-at-home care.

The Bologna Hospital-at-Home: a model for cost-effective care of advanced cancer patients in developing countries.

BACKGROUND: There are two options for India, if it intends to build up an adequate level of assistance for advanced cancer patients: increase the number of hospital beds (including hospice care); or introduce home care. We have used the home care approach in Italy and found it to be cost-effective. METHODS: Costs of the Bologna Hospital-at-Home (BHH) were analysed in 1992 (550 patients) and 1993 (152 patients). Direct and indirect costs were included; no intangible costs were found. The patient's perspective was also analysed. In 1995, an observational study was performed to determine the quality of life of patients admitted to two alternative care settings--the BHH and a traditional hospital, the Ospedale Sant' Orsola Malpighi (OSM), Bologna. RESULTS: Delivery of services was not different in both settings--the OSM and BHH. The analysis of satisfaction showed that 98% of the BHH patients surveyed felt it matched the actual needs. The quality of life was considered to be 'reduced/bad' in 67% of the OSM patients but in only 51% of BHH patients. With regard to transfer to the alternative setting of nursing, 47% of patients receiving care in the traditional hospital felt that hospital-at-home care would be better. The daily costs for BHH patients ranged between US$ 63.9 and US$ 75.9. CONCLUSION: Hospital-at-Home care merits consideration in the palliative care of advanced cancer patients in developing countries. Detailed quality of life studies and cost-benefit assessments would need to be done before such a strategy is implemented. The BHH could be a model adaptable to developing countries. Our first experiences with such a model in Albania and India were encouraging.

Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

Chemotherapy of advanced ovarian cancer.

Majority of ovarian cancer patients have advanced disease (stage III or IV) at diagnosis and the prognosis of these patients is poor in spite of aggressive surgery. Therefore chemotherapy has gained a fundamental role in the therapeutic approach of ovarian cancer. Platinum compounds in combination with alkylating agents and taxoids have the higher antitumor activity in ovarian cancer, while the role of anthracyclines remains controversial. Our 10-year experience with cisplatinum-based polychemotherapy in 196 advanced ovarian cancer patients previously untreated with chemotherapy is reported. 74 patients were treated with the combination cis-platinum and anthracyclines; 53 patients received the combination cis-platinum plus epirubicin alternated to cyclophosphamide plus 5-fluorouracil; 48 patients were treated with cis-platinum plus cyclophosphamide plus epirubicin and 21 patients were treated with the same combination with intraperitoneal administration of cisplatin. Our data confirm literature results of 55% remission rate, with 29% showing complete remissions. The median survival was 79 weeks and the overall 10-year survival was 13%. Complete responders had a median survival of 263 weeks and a 30% survival at 10 years. The main prognostic factors in our retrospective analysis were the objective remission, the size of residual tumor, the performance status and the stage. With the combination carboplatin (300-400 mg/sm) and cyclophosphamide (600 mg/sm) we observed 80% objective responses (23% complete responses) in 53 advanced ovarian cancer patients. The median overall survival in this group was 140 weeks. We carried out a phase II, non-randomized study of taxol in 54 ovarian cancer patients pretreated with platinum-compounds. The overall tolerability was good and an objective remission was observed in 47% of cases (8% complete remissions). The median survival was 68 weeks. As a consequence of our previous experience, a phase I dose-finding study with the combination carboplatin and taxol was started in our Division in 1994. Up to now, 22 chemotherapy untreated patients entered the study and the 5th dose level (taxol 175 mg/sm and carboplatin 350 mg/sm) has been completed without reaching the maximum tolerated dose. Our preliminary data suggest that the combination taxol-carboplatin is very active as the first-line chemotherapy in advanced ovarian cancer (73% objective remissions in 15 evaluated patients).

[Home hospital for advanced stage cancer patients: costs and benefits]. / Homehospital für Krebskranke im fortgeschrittenen Stadium: Kosten und Nutzen.

15,290 patients have been treated in the Bologna home hospital (BHH) until June 30, 1996. The average daily costs in BHH were estimated as 118789 Liras (ranging from 108 569-129027 Lire depending on the nursing category). Care intensity and patient's quality of life in the BHH are high. 98% of patients were content with the setting in which they were nursed. A questionnaire on the degree of satisfaction with the care was completed by 134 BHH patients and 102 patients of Division Oncologia Medica. Azienda Ospedaliera Sant, Orsola Malpighi, Bologna. Satisfaction with respect to sleeping, meals and family communications was expressed more often by BHH patients. Less patients of the BHH evaluated "quality of life" reduced or bad (51% vs. 67%) or requested a transfer to the alternative setting (03% vs. 47%). Advocating step by step introduction of home care, quality of life aspects have priority. Certainly, home care deserves greatest attention providing care during the life with cancer. However the final decision about the settings of nursing has to be made by the patients themselves in accordance with his understanding of quality of life.

Home artificial nutrition in advanced cancer.

Attitudes to home artificial nutrition (HAN) in cancer vary greatly from country to country. A 6-year prospective survey of the practice of HAN in advanced cancer patients applied by a hospital-at-home programme in an Italian health district was performed to estimate the utilization rate, to evaluate efficacy in preventing death from cachexia, maintaining patients at home without burdens and distress and improving patients' performance status, and to obtain information about costs. Patients were eligible for HAN when all the following were present: hypophagia; life expectancy 6 weeks or more, suitable patient and family circumstances; and verbal informed consent. From July 1990 to June 1996, 587 patients were evaluated; 164 were selected for HAN (135 enteral and 29 parenteral) and were followed until 31 December 1996. The incidence of HAN per million inhabitants was 18.4 in the first year of activity and 33.2-36.9 in subsequent years, being 4-10 times greater than rates reported by the Italian HAN registers. On 31 December 1996, 158 patients had died because of the disease and 6 were on treatment. Mean survival was 17.2 weeks for those on enteral nutrition and 12.2 weeks for those on parenteral nutrition. Prediction of survival was 72% accurate. 95 patients had undergone 155 readmissions to hospital, where they spent 15-23% of their survival time. Burdens due to HAN were well accepted by 124 patients, an annoyance or scarcely tolerable in the remainder. The frequency of major complications of parenteral nutrition was 0.67 per year for catheter sepsis and 0.16 per year for deep vein thrombosis. Karnofsky performance score increased in only 13 patients and body weight increased in 43. The fixed direct costs per patient-day (in European Currency Units) were 14.2 for the nutrition team, 18.2 for enteral nutrition and 61 for parenteral nutrition. The results indicate that definite entry criteria and local surveys are required for the correct use of HAN in advanced cancer patients, that HAN can be applied without causing additional burdens and distress, and that its costs are not higher than hospital costs.

A new regimen of cisplatin, epirubicin and methotrexate (PEM-3) as primary chemotherapy for locally advanced bladder cancer.

In this phase II study, 41 patients with locally advanced urothelial bladder cancer (T2-4, N0, M0) were treated with primary chemotherapy (cisplatin, epirubicin, methotrexate: PEM-3). All the patients were assessable for response and toxicity. Clinical monitoring was performed with computerized tomography and cystoscopy. Nineteen clinical complete remissions (46%) and 10 partial remissions (24.5%) were obtained (CR + PR, 70.5%; 95% confidence interval, 57%-85%). Ten patients were considered to have clinically stable disease (24.5%), and 2 patients progressed (5%). Surgery after chemotherapy was performed in 22 cases: in 6 patients (27%) a pathologic complete response was achieved. The pathologic stage was lower than the initial clinical stage in 13 patients (59%). After a median follow-up of 3 years (range, 1-4), the median time to progression was 104 weeks. At this writing, 20 patients, 12 of which were submitted to surgery and 8 were not operated, are disease-free. The 3-year survival rate is 52%. No one had to interrupt the treatment because of toxicity. In conclusion, the PEM-3 regimen is a very active and well-tolerated regimen in locally advanced bladder cancer.

An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens.

The aim of the study was to compare granisetron (GRA) with ondansetron (OND) in the prevention of acute emesis in consecutive chemotherapy-naive patients admitted to our department to receive a cytotoxic treatment containing cisplatinum (CP) at a dose > or = 50 mg/m2. Eligible patients were randomised at their first cycle to receive either OND or GRA with cross-over of the anti-emetic treatment on the second cycle. The cytotoxic treatments included five different multidrug regimens containing CP (median dose 60 mg/m2, range 50-70 mg/m2) administered on day 1 and repeated every 21-28 days. OND was administered at the dose of 8 mg x 3 i.v. on day 1 and 8 mg x 2 orally on day 2. GRA was always administered at the dose of 3 mg i.v. on day 1. 124 patients entered the study. 58 patients received OND at their first cycle and 66 received GRA. Complete protection of acute emesis with OND and GRA was observed, with the first and second cycles combined as follows: nausea 53 and 60%, vomiting 68 and 71%, respectively (no statistically significant difference). The cross-over analysis comprising 101 patients confirmed no difference between the two anti-emetic treatments. 21 patients (19%) on OND and 14 patients (12%) on GRA suffered headaches (P = 0.15). 25 (25%) patients preferred OND, 45 (45%) preferred GRA, while 31 (30%) expressed no preference (P = 0.003). However, these differences also depended on the sequence of anti-emetics in the cross-over. In conclusion, in this study, a single dose of GRA is demonstrated to be as effective as multiple doses of OND in the prevention of acute emesis.