6145 Background: The transition from curative to palliative care is a difficult phase in the illness trajectory of many oncologic patients (pts). Change of the health care professionals involved in EoL assistance may result in a sense of abandonment for pts and families. Methods: A semistructured telephone interview was conducted by two psychologists on relatives of pts who died between 01/2008 and 06/2009 (time from death ranged between 6 and 24 months). Research questions focused on the last month of life and included oncologist's involvement, sense of abandonment if the patient-oncologist relationship was lost, satisfaction with the quality of care (measured with a five-point scale: poor, fair, good, very good, excellent; and converted to a 0-to-100 scale) and oncologist's involvement in bereavement activities. A final open-ended question addressed suggestions for improvement. Results: Fifty-eight patient's relatives were contacted, 50 accepted the interview (32 spouses, 14 children, 3 in-laws, 1 nephew). Twenty-two pts had died at home, 28 in hospital. In 39 (78%) cases the oncologist-patient relationship was maintained in the last month of life, and this continuity was highly appreciated by the family. For the 11 pts (26%) who lost contact with their oncologist, a sense of abandonment was reported only in one case; in all other cases there was a closure of the patient-physician relationship that prevented feelings of abandonment. While the mean score of overall satisfaction relative to the quality of care in the last month of life was 61, this score dropped to 34 for pts who were no longer followed by their oncologist. Only in 13 (26 %) cases there was a post-mortem communication between the family and the oncologist, always on the family's initiative. Every relative interviewed expected at least a phone call from the oncologist. Conclusions: Continuity of care at the EoL is a priority issue for the families of cancer pts. The daily routine of palliative care and hospice facilities should involve the oncologist to improve the experience of care. Patients' families expect a commitment by the oncologist in bereavement activities. No significant financial relationships to disclose.

Background: In a previous dose-finding trial, in previously treated patients with metastatic breast cancer (MBC), we showed that the combination of Mitoxantrone (M) and Paclitaxel (P) may be an interesting (response rate: 69%) and well-tolerated regimen. On the basis of these results, Our group started a new trial in chemotherapy-naive patients with MBC. Patients and Method: Forty-six women entered in this trial, and all patients were evaluated for response and toxicity. Schedule of treatment was P 175 mg/m(2) over 3 hr day 1 and M 12 mg/m(2) day 1, every 3 weeks. Patients were reevaluated every 3 months and chemotherapy was continued unless tumor progression or unacceptable toxicity occurred. Result: The intent-to-treat objective response was 61% (95% confidence interval: 49%-78%). Five patients (11%) obtained complete response and 23 (50%) partial response with a median time to failure of 14 months. The median survival was 22 months (range 1 -39). The principal toxicity was hematological: 38 (82%) patients had grade 3 to 4 leukopenia; only 2 patients had grade 4 anemia and one grade 4 thrombocytopenia. Nonhematological toxicity (grade 3-4) was mild and cardiotoxicity was infrequent. Conclusion: This trial suggests the combination of M and P is an active palliative regimen for patients with MBC. Toxicity was moderate. The infrequent development of cardiotoxicity suggests this combination may not share the problems reported with P plus doxorubicin combinations.

This study aimed to verify whether the advantage in terms of response rate and survival of dacarbazine plus tamoxifen over dacarbazine alone in metastatic malignant melanoma reported in a previous randomized trial was due to a specific interaction of dacarbazine with tamoxifen. A total of 125 patients with locoregional or disseminated malignant melanoma were randomized to receive dacarbazine (250 mg/m(2) days 1 -5 every 3 weeks) plus tamoxifen (arm A) or vindesine (3 mg/m(2) every week for 6 weeks, then every 2 weeks) plus tamoxifen (arm B). Of the 125 randomized patients, 57 and 59 were evaluable in arm A and B, respectively. The complete response rates were the same (2% versus 2%) and the complete plus partial response rates were similar (11% versus 14%) in the two groups. There was no significant difference in survival. Neither response or survival correlated with gender. In conclusion, when combined with tamoxifen, dacarbazine does not have a specific effect on response or survival compared with vindesine. The lower response rate to dacarbazine plus tamoxifen (11%) than that reported in the previous trial (28%) might be explained by actual differences in patient and/or participating centre accrual characteristics in the presence of apparently identical eligibility criteria.

The Italian Oncology Group for Clinical Research tested two experimental chemotherapy strategies in an attempt to improve the results achievable with conventional chemotherapy in metastatic breast cancer. One hundred sixty-two patients were randomly allocated as follows: (a) to the conventional cyclophosphamide, methotrexate, 5-fluorouracil chemotherapy regimen (CMF); (b) to a rotational crossing program (ROT-CROSS); or (c) to a sequential intensification program (SEQ-INT). The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy. The SEQ-INT program induced a significantly higher complete response (32% vs. 6%, p= 0.0006) and objective response rate (72% vs. 42%, p= 0.0047) than CMF did. There were no differences in survival between CMF and either experimental arm. A number of side effects were significantly more with both experimental chemotherapies than with CMF, but the treatments were generally tolerable. Although some caution is required when interpreting a significant advantage found between an entire chemotherapeutic strategy and a single conventional combination, this study documents the potential therapeutic advantage of administering different sequential chemotherapies, and changing each at the time of maximum result without waiting for a progression. The impressive cytoreductive effects achievable with this policy (SEQ-INT) in metastatic disease merit further investigation in the adjuvant setting.

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.].

Bisphosphonates are used in oncology as a means of decreasing complications due to bone metastases, in association with anticancer treatment, especially in patients with breast cancer, prostate cancer and myeloma. Little is known about the effects of bisphosphonates on bone metastases from other tumors and in particular from tumors for which no effective treatment is available. We conducted a randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone metastases from tumors poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone metastases evolution. Sixty-six patients with poorly responsive tumors such as non-small cell lung cancer (NSCLC), bladder cancer, gastrointestinal cancers, kidney cancer, melanoma and metastatic carcinoma of unknown origin entered the study. Patients were randomized to receive either clodronate 1,600 mg/day for one year or identical placebo-containing tablets. Various parameters such as Karnofsky performance status, pain score (measured by a visual-analogue scale) and analgesic requirement were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be adequately evaluated. At 3 months both clodronate and placebo-treated patients had a decrease in Karnofsky performance status, with the decrease being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to be statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p = 0.042), in whom increase in opioid requirements was particularly evident. Toxicity was low, with occasional gastroenteric discomfort in both groups. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, and approximately 25% of the 66 enrolled were not considered evaluable; few patients survived for the length of the study, one year. This might partly account for the lack of significance of some of the parameters under study. With these limits, oral clodronate demonstrated some efficacy in symptom control and in reducing the need for analgesics.

In this study we evaluated the antiemetic activity of a combination of 3 mg granisetron in a short i.v. infusion followed by 12 mg dexamethasone i.v. in 64 patients with cancer receiving moderately emetogenic chemotherapy scheduled in a single day. No patient had previously undergone chemotherapy and three consecutive cycles were evaluated. Response to antiemetic treatment was graded as follows: complete response, no episodes of vomiting; major response, only one episode; minor response, two to four episodes; failure, more than four episodes. Nausea was graded as absent, mild, moderate or severe (patients bedridden). At the first cycle a complete protection from acute vomiting and nausea was achieved in 95% and 73% of patients respectively; the rate of complete response for delayed vomiting was 90%, while 45% of patients complained of delayed nausea. The antiemetic and antinausea efficacy remained substantially unchanged during the second and third cycles of chemotherapy. Constipation and headache were the most frequent adverse events. In conclusion this antiemetic regimen appears very effective in preventing nausea and vomiting in moderately emetogenic chemotherapy.

With the association of 5-fluorouracil (5-FU) and alpha-interferon (IFN), objective responses as high as 26 63% have been reported in untreated patients with advanced colorectal cancer. However, grade 3-4 toxicity has also been reported. We have conducted a prospective phase II randomised study comparing 5-FU to 5-FU + IFN, to investigate whether the addition of IFN to a weekly 5-FU regimen devoid of significant toxicity used at our institutions could improve the effectiveness of 5-FU while maintaining acceptable toxicity. Patients with histologically proven advanced colorectal carcinoma were randomised to receive 5-FU 500 mg m-2 intravenous (i.v.) bolus on days 1-5 followed by 5-FU 500 mg m-2 i.v. bolus weekly from day 15, with or without IFN alpha-2a intramuscularly (i.m.) 1.5 mU daily on days 6-12 and 3 mU i.m. daily thereafter. The treatment was administered on an outpatient basis. Response was evaluated every 3 months, and treatment continued until progression or after two consecutive judgements of stable disease. Response rate was the main end point of the study. Of 141 patients eligible, 72 were randomised to 5-FU alone (arm A) and 69 to 5-FU + IFN (arm B). Responses were 9/72 (12.5%) in arm A and 6/69 (8.7%) in arm B; complete responses were three in arm A and two in arm B. Progression-free survival (median 4 months) and survival (median 12 months) were identical in the two arms. Toxicity was almost absent in arm A and moderate in arm B, represented mainly by haematological toxicity (usually leucopenia). In conclusion, overall survival was good in both arms of treatment and toxicity was moderate. While the response rate with 5-FU alone was in accord with the literature data, response to 5-FU + IFN was lower than expected. At least at this dosage and schedule, the association of 5-FU and IFN is no better than 5-FU alone and is of no clinical interest.

The Italian Oncology Group for Clinical Research (GOIRC) randomized 55 naive patients with advanced pancreatic cancer (APC) between intravenous fluorouracil (5FU) 400 mg/m2, days 1-5 and folinic acid (FA) 200 mg/m2, days 1-5 alone, using Machover's schedule, or with FU, FA, and ifosfamide (IFO) 5 g/m2, day 1 and Mesna. In both arms, treatment was repeated every 28 days. Fifty-one patients were evaluable for response. The overall response rate was 6% (3 out of 51), 1 out of 29 (3%) complete response (CR) in the arm with FU plus FA, and 2 out of 22 (9%) partial responses (PR) in the arm with IFO. The duration of response rate was 39, 55, and 74 weeks, respectively. Median survival time was 21 weeks (range, 4-83 weeks) for 5FU/FA and 16 weeks (range, 3-106 weeks) for the FU/FA/IFO arm. Diarrhea, mucositis, and vomiting occurred in the majority of patients. One patient died due to toxicity. The combination of 5FU plus FA failed to demonstrate therapeutic activity in patients with APC and was associated with moderate to severe toxicity that could lower the quality of life of these patients. Ifosfamide did not potentiate the activity of this combination. Neither of these combinations should be considered for treatment of patients with APC.

The clinical record of 136 patients with unknown primary tumors (UPT) were reviewed. Seventy-four cases were initially diagnosed as adenocarcinoma, 45 as carcinoma, whilst in 16 cases other hystologies were found; the most frequent sites of initial biopsy were lymph nodes (30.9%), bone (12.5%), central nervous system (12.5%), soft tissues (11.8%) and liver (11.0%). The extent of diagnostic work-up and the type of treatment were not uniform and were individually tailored to fit clinical presentation. In general, the search for the primary tumor was extensive though fruitless: this diagnostic perseverance lead in most cases to delayed treatment. Seventy-six patients were treated with different chemo and/or radiotherapy schemes. Median survival time was 6 months for all patients with 22/136 patients alive at 2 years and 3 patients alive at 5 years; factors influencing prognosis were initial performance status, single vs multiple metastases, nodal vs visceral involvement. The site or origin was established in 21 cases, 18 of which by autopsy. The commonest sites of origin were lung (7/21), and liver (4/21). Among these 21 patients, 8 were found affected by neoplasms for which effective treatment exists, including two lymphoproliferative diseases. Our data do not support individualized diagnostic and therapeutic procedures for UPT patients, and suggest the need for a standardized approach, with an improved balance between diagnosis and treatment: limited instrumental and invasive procedures, accurate histopathologic characterisation, prompt institution of treatment.