Screening elderly cancer patients for disabilities: evaluation of study of osteoporotic fractures (SOF) index and comprehensive geriatric assessment (CGA).

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional tool aimed at detecting multiple age-related problems; the study of osteoporotic fractures (SOF) index is a 3-item instrument designed to measure frailty and pre-frailty status. The aim of this prospective cohort study was to evaluate the accuracy of the SOF index and CGA in predicting the disability status in elderly cancer patients. PATIENTS AND METHODS: Patients aged ≥ 70 years with a confirmed diagnosis of a solid or hematologic tumor underwent both CGA and SOF assessment. The sensitivity and specificity of SOF in determining the presence of frailty were analyzed using the CGA as the reference standard. The diagnostic accuracy of SOF < 80% was considered not acceptable. RESULTS: The study involved 400 patients aged ≥ 70 years (median age 77.2, range 70-97).The SOF and CGA classified, respectively, 33.2% and 31.8% of patients as fit, 67.8% and 68.2% as unfit. The SOF showed a sensibility and a specificity of 89.0 [95% confidence interval (CI) 84.7-92.5] and 81.1 (73.2-87.5) with an accuracy of 86.5 (82.8-89.7). The negative predictive value (NPV) was 103/133, i.e. 77.4% (95% CI 69.4-84.2). CONCLUSIONS: As the SOF proved to reach the end-point of our study, we support its use as a means of screening elderly cancer patients in everyday clinical practice.

Clinical analysis of multiple primary malignancies in the elderly.

BACKGROUND: Cancer incidence raises progressively during life span; it is estimated that by the year 2030 almost 70% of all neoplasms will occur in people over 65 years old. As carcinogenesis is a multistep, time-requiring process, it is expected that as people live longer they are more likely to develop cancer, and therefore, the prevalence of multiple primary malignancies (MPM) is destined to increase with age. PATIENTS AND METHODS: Records of all consecutive cancer patients referred to our center from January 2004 to January 2007 were reviewed. We chose the definition of MPM proposed by Warren and Gates. Multiple malignancies were assessed for elderly (>or=70 years old) and younger patients. t-Test and Mc Nemar test were used; subgroup analysis was also performed according to age stratification. RESULTS: A total of 1,503 consecutive patients were considered; 566 were 70 years old or more (mean age 76.5 years, range 70-96 years) and 878 were younger (mean age 57 years, range 18-69 years). The prevalence of multiple malignancies in the elderly people versus younger ones was 15% and 6%, respectively (P = 0.001). As far as the elderly population is concerned, 21% (56/271) of males compared with 14% (42/295) of females had developed MPM; no significant difference was found between the subgroups with MPM or not as far as age (P = 0.16), comorbidities (P = 0.79), medications (P = 0.76), CIRS-G score and index (P = 0.47, P = 0.54), and PS (P = 0.93) are concerned. Most frequent associations among cancer types were prostate with lung (10/87, 11%), prostate with colorectal cancer (10/87, 11%), and smoking-related cancer, namely lung and head and neck cancer (X/Y, 6%). CONCLUSIONS: Elderly patients are more likely to develop MPM compared to younger ones. Significant cancer association according to field cancerogenesis concept was the one of smoking-related cancer; other MPM patterns were apparently a random phenomenon.

Do elderly cancer patients achieve an adequate dose intensity in common clinical practice?

BACKGROUND: Elderly patients rarely receive adequate dose intensity (DI) using conventional regimens. Possible causes are improper patient assessment, the chemotherapy (CT) regimen chosen, the number and severity of comorbidities, patient compliance and physician experience. To explore this issue, DI was retrospectively analyzed in elderly patients treated with conventional CT regimens for advanced solid cancer. PATIENTS AND METHODS: Patients > or =69 years were evaluated. All patients had metastatic solid tumors. Comorbidities, performance status (PS), toxicities, number of CT cycles, dose reduction and discontinuation of treatment were recorded. Relative DI (RDI) was calculated and regressed against these parameters. RESULTS: 108 patients were eligible. The most frequent diagnoses were: lung, head-and-neck and colorectal cancer. In 48 patients (44%), their initially scheduled treatment was modified. Mean RDI was 79% (range 19-100%, SD 20.6). Grade 3/4 non-hematological and hematological toxicity occurred in 27 (35/130) and 8% of patients (11/130), respectively. In regression analysis, RDI was significantly associated with hematological toxicity. RDI affected response rate but not overall survival. CONCLUSIONS: RDI is significantly affected by toxicity. These data suggest the importance of the treatment schedule and patient selection as predictorsof adequate treatment. Some non-ratable variables, however, might also play a role regarding the dose intensity delivered.

Phase I clinical and pharmacokinetic studies of the taxoid derivative RPR 109881A administered as a 1-hour or a 3-hour infusion in patients with advanced solid tumors.

PURPOSE: To define the maximum tolerated dose (MTD), the recommended phase II dose, the optimal infusion duration and pharmacokinetics of the semisynthetic taxoid derivative RPR 109881A, given as a 1-h or 3-h infusion every 3 weeks. PATIENTS AND METHODS: RPR109881A was administered as a 1-h i.v. infusion to 34 patients (study 1) with oral steroids as pre-medication. In a subsequent study, 29 patients were treated at the recommended dose or at the dose immediately below (study 2); the first 14 patients received RPR 109881A as a 3-h infusion, while the subsequent 15 were randomized to receive the drug as a 1-h or 3-h infusion. The pharmacokinetics of RPR109881A was studied in plasma and urine and for selected patients in some biological fluids (cerebrospinal fluid, pleural effusion, ascitis). RESULTS: In study 1, the dose was escalated from 15 to 105 mg/m(2), at which dose two of five patients presented dose-limiting toxicities with febrile neutropenia (FN) after the first cycle, thus defining the MTD. The dose of 90 mg/m(2), at which grade 3/4 neutropenia was almost universal with FN in 18%, was recommended for phase II. At 90 mg/m(2) the incidence of diarrhea, fatigue and alopecia were 59, 29 and 70%, respectively. The results of study 2 were comparable to those of study 1, thus recommending the 1-h infusion duration for phase II evaluation. RPR 109881A exhibited a high total body clearance, a large distribution volume and long terminal half-life of 20 h. RPR 109881A was detected in cerebrospinal fluid shortly after the end of 1-h infusion. Three objective responses were observed in non-small-cell lung cancer (NSCLC) patients, including a patient with brain metastases. CONCLUSIONS: The antitumor activity in NSCLC, the reproducible profile of toxicity and above all the ability to cross the blood-brain barrier make RPR 109881A worthy of further disease-oriented clinical development.

Preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels as prognostic indicators in resected non-small cell lung cancer.

In 62 patients affected by resectable non-small cell lung cancer (NSCLC) submitted to radical surgery we evaluated the prognostic significance of CEA, NSE, SCC, TPA, and CYFRA 21.1 serum levels at diagnosis, as well as the predictive ability of these tumor markers with respect to histological type and pathological stage. The group was composed of 56 male and 6 female patients; the median age was 62 years (range 29-73 years). Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinoma; with regard to pathological stage, 32 patients had stage 1, 4 patients stage II and 23 patients stage IIIA disease. A good predictive ability with respect to histological type was obtained with SCC serum levels; as for pathological stage, TPA and CYFRA 21.1 were found to have moderate predictive ability. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at diagnosis were reliable predictors of overall survival, high values of these markers being associated with a worse prognosis.

Tumour markers CEA, NSE, SCC, TPA and CYFRA 21.1 in resectable non-small cell lung cancer.

BACKGROUND: In the last few years, several prognostic factors have been investigated in order to identify among patients with completely resected non-small cell lung cancer (NSCLC) subsets at high risk of recurrence. In this context, the actual role of serum tumour markers is still unclear. The aim of this study was to evaluate the prognostic significance of preoperative CEA, NSE, SCC, TPA and CYFRA 21.1 serum levels in 62 patients submitted to radical surgery for non-small cell lung cancer (NSCLC). The predicting ability of these tumour markers with respect to histological type and pathological stage was also assessed. PATIENTS AND METHODS: After informed consent was obtained, the preoperative serum concentrations of the tumour markers CEA, NSE, SCC, TPA and CYFRA 21.1 were measured by means of immunometric assays in 62 patients referred to our Institutions from January to December 1992. All patients had resectable, histologically proven NSCLC and were submitted to radical surgery. Overall survival (OS) was calculated as the time elapsed from surgery to the date of death or last clinical evaluation; the prognostic effect of the tumour markers was investigated by Cox multiple regression models. RESULTS: Fifty-six patients were male and 6 female; median age was 62 years. Thirty-four patients had a histological diagnosis of adenocarcinoma and 28 of squamous cell carcinomas. With regard to pathological stage, 32 patients had stage I, 4 patients had stage II and 23 patients had stage IIIA disease. In this series of patients, at a median follow-up of 55 months after surgery, we found that both TPA and CYFRA 21.1 serum levels at the time of diagnosis were reliable predictors of overall survival high values of these markers being associated with worse prognosis. CONCLUSIONS: Our findings suggest that in completely resected NSCLC, TPA and CYFRA 21.1 preoperative serum levels might provide a useful tool for stratifying subgroups of patients with different chances of disease recurrence after surgery.

Long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a in polycythaemia vera.

We report on long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia vera (PV). In all patients haematocrit was first brought into the normal range by venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU. Complete response (CR) was defined as persistence of normal haematocrit without venesection and partial response (PR) as >50% reduction of phlebotomy requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median duration of treatment for all responsive patients was 40 months; 12 patients are still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50, 51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN-alpha also normalized leucocyte counts, platelet counts and spleen enlargement; rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment suspension in all cases. Progression to leukaemia was observed in none of the 10 patients treated only with rIFN-alpha and in one of the 12 who received alkylating agents before enrolment in this study. According to these data, rIFN-alpha seems to be an effective and safe treatment option for PV.

Polycythemia vera treated with recombinant interferon-alpha 2a: evidence of a selective effect on the malignant clone.

We periodically analyzed bone-marrow cytogenetic features in 8 patients belonging to a series of 38 subjects with polycythemia vera (PV), all treated with recombinant interferon-alpha 2a (rIFN-alpha) at a weekly dose of 9,000,000 IU. Six out of these 8 patients never showed any chromosome alterations, while 2 displayed at diagnosis the presence of trisomy 8 in all bone-marrow metaphases. Interestingly enough, in these 2 patients rIFN-alpha treatment was able to induce not only complete hematological response but also the disappearance of trisomy 8, as shown by conventional cytogenetic investigation and fluorescence in situ hybridization performed on bone-marrow cells after 1 year of treatment. This finding indicates that, as previously shown in chronic myeloid leukemia, in PV rIFN-alpha can also eradicate the malignant clone by means of a selective effect on bone-marrow transformed cells.

Fluorescence in situ hybridization (FISH) for evaluating residual disease in Philadelphia chromosome-positive chronic myeloid leukemia during interferon alpha therapy.

Fluorescence in situ hybridization (FISH) is a quantitative technique which allows, by means of specific probes, to detect the t(9;22) translocation typical of chronic myeloid leukemia (CML) hematopoietic cells. We have evaluated FISH on interphase nuclei as a method for assessment of residual disease in bone marrow samples from 5 Philadelphia chromosome positive (Ph(+)) CML patients after 12 months therapy with interferon alpha; results were compared with findings obtained by conventional cytogenetics and by polymerase chain reaction (PCR). Our data indicate that FISH is more sensitive than cytogenetics for evaluation of residual disease, being positive in 1 out of 2 cases scored as Ph negative by cytogenetics, but is less sensitive than PCR which turned out to be positive in all patients. As additional advantage over conventional cytogenetics, FISH on interphase nuclei can be performed also on samples lacking metaphases or having poor chromosome spreading or unsatisfactory chromosome banding.

Chronic myeloid leukemia treated with busulfan.

Interferon alpha is presently viewed as the first choice drug for treatment of chronic myeloid leukemia; however patients who are not eligible for this type of therapy are still treated with conventional chemotherapeutic agents as for instance hydroxyurea and/or busulfan. In a series of 23 patients with Philadelphia chromosome positive chronic myeloid leukemia who have been treated solely with busulfan, we have evaluated the relationship between total amount of drug required during the first 12 months of treatment and duration of the chronic phase. A statistically significant (p<0.005) inverse relationship between these two parameters was found, indicating that patients with low busulfan requirement during the first year of therapy have a better prognosis.