Search

Adjuvant treatment of elderly women affected by breast cancer who have a high risk of recurrence is one of the most questionable issues in clinical oncology. The use of tamoxifen in women with hormone receptor-positive tumors is a relatively simple therapeutic option considering the favourable toxicity profile, whereas the administration of adjuvant chemotherapy is more complicated and a variety of aspects need to be considered. The estimated life expectancy, the presence and degree of comorbid conditions, the geriatric assessment and estimated benefit from treatment should be taken into account. Due to the lack of data from clinical trials in women over the age of 70, the approach is still experimental. Clinical trials evaluating the role of adjuvant chemotherapy in high risk patients are currently being developed and hopefully in the near future, more convincing data on the best drugs, regimens and benefits for the treatment of elderly breast cancer patients will become available.

Aims and Background: Ifosfamide is an active drug in advanced breast cancer. Short-term continuous infusion schedules have been evaluated with encouraging results. The aim of the study was to evaluate in patients with advanced breast cancer a 14-day infusion schedule previously tested at our center in soft tissue sarcomas., Methods: From July 1998 to February 2000, 26 consecutive patients with heavily pretreated breast cancer, progressing during protracted continuous infusion of fluorouracil, were treated with ifosfamide at the dose of 800 mg/m2/day for 14 consecutive days by means of an elastomeric pump via an in-dwelling Groshong catheter. The median age of the patients was 52 years (range, 32-67) and median PS was 1 (range, 1-3). All patients were pretreated with anthracyclines or taxanes; the median number of chemotherapy lines in the metastatic phase was 2 (range, 1-4). Predominant metastatic sites wen soft tissues in 5 patients, lung in 6, liver in 7 and serosal cavities in 3., Results: Twenty-four patients were assessable for response Two complete responses and 2 partial remissions were noted for an overall 16.6% response rate. The duration of response was 3+, 5, 8 and 10 months, respectively. Stabilization or mi nor response was observed in 2 more patients. The main tox ic effect was myelosuppression (grade 1-2 in 15 patients grade 3-4 in 4). Other toxicities included nausea in 14 patients (grade 3 in 2) and grade 1-2 vomiting in 2 patients. Hair lost or alopecia was universal., Conclusions: The regimen yielded some clinically useful re sponses with acceptable toxicity. Its evaluation in less ad vanced cases appears to be warranted.

Aims and Background: The evaluation of unconventional schedules of well-known drugs represents a promising avenue in the search for new regimens with a better therapeutic index in metastatic breast cancer. In particular, protracted continuous infusion (PCI) of 5-fluorouracil (5-FU) has yielded interesting results in gastrointestinal malignancies and in breast cancer., Methods: From March 1996 30 consecutive patients with heavily pretreated breast cancer were treated with PCI 5-FU at a daily dose of 250 mg/m2 by means of disposable elastomeric pumps until progression or toxicity. The median age was 54 years (range, 28-71) and median performance status was 1 (range, 0-3). All patients but four were pretreated with anthracycline-containing regimens or taxanes; the median number of chemotherapy lines was 3 (range, 2-4). Metastatic sites were predominantly visceral in 60% of the patient population., Results: All 30 patients were evaluable for response and toxicity. The median duration of PCI was 20 weeks (range, 2-36 weeks). Two complete responses (7%) and eight partial remissions (26%) were observed, giving an overall response rate of 33%. The median duration of response was six months (range, 4-9 months). Stabilization was observed in seven patients (23%) with a median duration of seven months (range, 3-9 months). The main toxic effects were grade I-II mucositis and hematologic toxicity, while grade 3 hand-foot syndrome was observed in eight patients (27%)., Conclusions: This study confirms the efficacy and safety of 5-FU at this dosage and schedule in heavily pretreated women with advanced breast cancer. In order to improve on these results further studies are needed in a less advanced stage of the disease and together with other active drugs.

The heritable defects of BRCA1 and BRCA2 genes have been shown to predispose to breast and ovarian cancers. In a previous report, we analyzed 46 Italian families with breast and/or ovarian cancer for BRCA1 mutations. In the present study, those families and 11 others were screened for BRCA2 mutations; the newly enrolled families were also analyzed for the BRCA1 gene. The coding region and splice boundaries of BRCA2 and BRCA1 genes were assessed by the protein-truncation test and single-strand conformational polymorphism. A total of 20 different mutations were found in 21 families (37%). A total of 9 families (16%) showed mutations in the BRCA1 gene, including the one new mutation identified in this study (5382insC), and 12 families (21%) presented mutations in the BRCA2 gene. BRCA2-mutated families presented breast and ovarian cancers or breast cancers only, whereas most BRCA1-mutated families presented ovarian cancer alone or in association with breast cancer. All the BRCA2 mutations led to a truncated protein: 6 were frameshift mutations, 4 were non-sense mutations and 2 involved the intronic invariant region leading to splice variants. Therefore, in the Italian population, the cumulative proportion of BRCA1 and BRCA2 mutations was within the range observed in other studies (37%), with higher involvement of BRCA2 than of BRCA1. Many families in which no mutations were found presented a very high incidence of breast and/or ovarian cancer. Among the 36 BRCA1 and BRCA2 wild-type families, 24 presented at least 4 cancer cases, indicating the existence of other important predisposing genes., (Copyright 1999 Wiley-Liss, Inc.)

Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCA1 mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron I was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCA1 mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCA1 in families with only breast cancers was 9%. In the 46 Italian families studied, BRCA1 mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCA1 genetic testing mainly when ovarian cancer is present.

Aims and Background: The aim of the study was to evaluate the impact of information level on quality of life in cancer patients previously studied for their information level., Patients and Methods: The information level was determined by means of a questionnaire that explored the degree of information on diagnosis and status of disease, the patient's interpretation of his/her disease status, and his/her satisfaction with the information received. Quality of life was evaluated, some months after evaluation of the information level, by means of the Functional Living Index for Cancer (FLIC) and the State-Trait Anxiety Inventory (STAI 1-2)., Results: A total of 175 patients were studied. Information was adequate in 53.7% of patients. An adequate level of information was present more frequently among patients aged < or = 65 years and in those patients followed at a cancer institute. There was no difference in the quality of life of adequately versus inadequately informed patients. Satisfaction with the information received influenced quality of life in both age groups. Objective clinical variables (active disease present and ongoing treatment) negatively affected quality of life in patients <65 years, whereas the subjective perception of the presence of disease was associated with a worse quality of life in older patients., Conclusions: In the study, although the level of information did not affect the quality of life, satisfaction with the information was associated with a better quality of life. The finding stresses the importance of a sensible disclosure of diagnosis and prognosis.

Aim: The aim of this study was to investigate whether tamoxifen toxicity and treatment discontinuations differed in the adjuvant versus chemopreventive setting., Methods: At our Institutions 119 postmenopausal breast cancer patients were randomized from August 1987 to March 1995 to tamoxifen only within adjuvant studies (International Breast Cancer Study Group studies VII and IX) and 202 healthy hysterectomized women aged 35-70 years were randomized from November 1993 to May 1996 in a multicenter, double-blind, placebo-controlled chemoprevention study (Italian Tamoxifen Prevention Study). The tamoxifen dose was 20 mg/day for 5 years in all studies. Median age was 66 years (54-85) in the adjuvant studies and 53 years (37-69) in the chemoprevention study. Median treatment duration was 238 and 120 weeks, respectively., Results: Patients treated within adjuvant studies experienced more hot flashes, vaginal discharge and/or bleeding, bone marrow depression and weight gain than those treated in the chemoprevention study, consistent with the fact that a proportion of women in the latter study were receiving placebo. Temporary discontinuation occurred in 2.5% of patients in the adjuvant studies and in 5.4% of women in the chemoprevention study (difference not statistically significant). Permanent discontinuation was more frequent in the chemoprevention study than in the adjuvant ones (26.7% vs 15.1%--P< 0.05)., Conclusions: In summary, our data show that, although the toxicity of tamoxifen is superimposable in the two settings, a larger proportion of women treated as chemoprevention discontinue treatment spontaneously. Due to the double-blind nature of the chemoprevention study, the impact of the toxicity of tamoxifen upon compliance in the chemopreventive setting cannot be ascertained.

The aim of this study was to investigate the activity and the toxicity of vinorelbine (VNB) in a population of patients with locally advanced inoperable or metastatic non-small cell lung cancer (NSCLC) including elderly patients unfit for cisplatin-based chemotherapy. VNB was administered at a dose of 25-30 mg/m2, intravenously, weekly until progression. Of the 83 patients who entered the study (median age 63 years, number of patients aged > or = 70 years = 23, median performance status = 80, stage IV in 58 patients, previous chemotherapy in 15 patients), 76 were evaluable. One complete remission and 22 partial remissions were noted (30.2% response rate). Toxicity was mild. Median survival was 9 months. No effect of age upon outcome was detected. Thus, single agent VNB is a reasonable option for advanced NSCLC, particularly in elderly patients.

From September 1986 until December 1991, 139 patients with histologically-proven small cell lung cancer, age < 75 years, performance status > 40, absence of brain metastases and no previous treatment, were randomised to receive either CEV cyclophosphamide 1000 mg/m2 intravenous (i.v.), epirubicin 70 mg/m2 i.v., vincristine 1.2 mg/m2 i.v., every 3 weeks or PE (cisplatin 20 mg/m2 i.v. and etoposide 75 mg/m2 i.v. for 5 consecutive days, every 3 weeks) for six cycles. After three cycles, responding patients received radiotherapy to the chest (45 Gy/15 sessions) and to the brain (30 Gy/10 sessions--only in patients with limited disease achieving complete remission). 3 patients were ineligible. Patient characteristics included (CEV/PE) total number 66/70, median age 60/61 years, median performance status 80/80, extended disease 33/48 cases (P = 0.04). In evaluable patients, 42/62 (67.7%) responded to CEV while 42/58 (72.4%) responded to PE (P = non-significant); respective complete response rates were 16.1 and 29.3% (P = non-significant) and respective complete response rates in patients with extended disease were 9.4 and 28.9% (P = 0.03). Median survival was 10.5 months, without significant differences in the two treatment arms, even after adjustment for stage. PE was less well tolerated than CEV. Although PE is more active than CEV in certain subsets of patients, its apparent inability to improve survival in this and in other studies questions its routine use in small cell lung cancer.

From May 1988 to March 1990, 17 consecutive patients with histologically proven malignant mesothelioma were treated with epirubicin 75 mg/sqm i.v. on day 1 and ifosfamide 1.8 gr/sqm/day i.v. from day 1-5. Treatment was repeated every 3 weeks until progression. Fifty-three chemotherapy cycles were administered to the 17 patients treated (median, 3 cycles/patient). No complete responses, 1 partial response, 8 stable diseases and 8 progressions were noted. Toxocity was acceptable and no treatment-related deaths occurred. Actuarial median survival was 6 months. In this study, a combination of full doses of epirubicin and ifosfamide did not prove to be active in malignant mesothelioma.

From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.

From January 1975 to June 1979 3,007 new patients have been followed in the Out-patient Clinic of the Division of Radiotherapy and Medical Oncology of the Ospedale Civile, Pordenone. A progressive increase in the number of patients and the validity of follow-up care has been demonstrated. Patients still encounter considerable logistic difficulties, which could be reduced by programming diagnostic procedures the same day of therapy. The organization of a drug service in the Out-patient Clinic, a more active collaboration with the sanitary units working outside the Hospital, and an adequate psychological assistance could solve many of the problems which are superimposed on the direct effects of the disease.

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS greater than 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS less than 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

We tested VP 16-213 in 16 patients with advanced head and neck cancer after conventional treatments. VP 16-213 was administered orally at the dosage of 100 mg/mq for 5 consecutive days every 3 weeks. No patient achieved an objective response. Toxicity was mild. VP 16-213 given at this dose and schedule revealed no activity in pretreated patients with head and neck cancer.

Forty-six evaluable postmenopausal patients with locally advanced, inoperable T3-T4 breast carcinoma were treated with tamoxifen 10-20 mg twice daily for a period at least 6 weeks. Eight patients (17%) had an objective response at the primary tumor site after 6 weeks of treatment. Improvement of response with a further single tamoxifen therapy was observed in 7 patients, resulting in an overall objective response in 14 of 46 (30%). Median duration of response was 8 months (range 2-24). No response was obtained in the 5 patients with inflammatory signs. Toxicity of treatment was minimal. Medial survival was 10 months (responders 17.5, non-responders 9). Tamoxifen seems to be safe and effective treatment for locally advanced breast cancer without inflammatory signs in postmenopausal women.

Carcinoembryonic antigen (CEA) assays (2536) were performed in 380 disease-free breast cancer patients after radical mastectomy. In the 334 evaluable patients with 3 or more determinations, the overall relapse rate after a median follow-up of 29 months was 11%. Of 203 patients with normal CEA values, 19 (9.3%) relapsed. In the 50 patients with the highest CEA value greater than 20 ng/ml, the relapse rate was 26%; in the 12 patients with gradually increasing CEA elevations it was 50%. However, CEA was unable to predict recurrence in N- patients. Premastectomy N+ was significantly associated with greater than 20 ng/ml or gradually increasing CEA values, suggesting the lack of an independent prognostic value of CEA in our patient population.

Twenty-seven evaluable patients with advanced head and neck squamous carcinoma were treated with a polychemotherapeutic regimen described in 1975 by Price et al. Chemotherapy consisted of vincristine, adriamycin, bleomycin, methotrexate, 5-fluorouracil, hydroxyurea, 6-mercaptopurine and citrovorum factor administered sequentially. One complete remission, 4 partial remissions, 7 minor responses were obtained for a total of 12/77 (44%) objective responses. Toxicity was acceptable. The results obtained were not better than those observed with less complicated regimens administrable on an outpatient basis.

From May 1980 to November 1981, 51 consecutive patients with locally advanced, recurrent or metastatic head and neck squamous carcinoma were treated with 2 successive outpatient chemotherapeutic regimens including adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and 5-fluorouracil with or without mitomycin-C. A 34% objective response rate was obtained with acceptable toxicity and good patient compliance. The presence of mitomycin-C did not influence response rate. Median survival was 9 months.