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BACKGROUND The aim of the current randomized Phase II study was to investigate the efficacy and safety of capecitabine combined with irinotecan as first-line treatment in metastatic colorectal carcinoma (CRC). METHODS A total of 140 patients received capecitabine at a dose of 1250 mg/m2 twice daily on Days 2–15 and irinotecan at a dose of either 300 mg/m2 on Day 1 (Arm A) or 150 mg/m2 on Days 1 and 8 (Arm B) every 3 weeks. During the course of the study, enrollment was continued using lower doses of capecitabine (1000 mg/m2 twice daily) and irinotecan (Arm A: 240 mg/m2; Arm B: 120 mg/m2) to improve the safety profile of the combinations. RESULTS Efficacy was evaluable in 134 patients (68 in Arm A, 66 in Arm B). Objective responses were observed in 46% of the patients (8% complete response [CR]), including 47% in Arm A (9% CR; 38% partial response [PR]) and 44% in Arm B (8% CR; 36% PR). The median progression-free survival was 8.3 months in Arm A and 7.6 months in Arm B. Among the first 52 patients treated with the higher doses, the most frequent Grade 3–4 adverse event was diarrhea (27%). The lower doses adopted in the subsequent 88 patients led to better diarrhea control, particularly in Arm A, and significant reductions in the incidence of all-grade hand-foot syndrome and abdominal pain. CONCLUSIONS The capecitabine and irinotecan combination was a highly active first-line therapy in metastatic CRC. An acceptable safety profile was observed after dose reduction, particularly when irinotecan was administered on 1 day. Cancer 2004;100:279–87. © 2003 American Cancer Society.

BACKGROUND: Aromatase inhibitors are more effective than is tamoxifen in prevention of breast-cancer recurrence, but at the expense of increased musculoskeletal side-effects, such as carpal tunnel syndrome. The aim of this study was to assess risk factors and the prognostic value of musculoskeletal symptoms during treatment with the steroidal aromatase inhibitor exemestane or with tamoxifen after 2-3 years of tamoxifen. METHODS: In the Intergroup Exemestane Study, postmenopausal women treated for early invasive breast cancer who remained disease free and on treatment after 2-3 years of tamoxifen were randomised to switch to exemestane or to continue tamoxifen for the remainder of the 5-year period of endocrine treatment. The primary endpoint for this retrospective analysis was occurrence of carpal tunnel syndrome and any musculoskeletal events, analysed in the safety population, which consisted of all patients who had received any trial treatment. As well as case-report forms, questionnaires were distributed retrospectively to gain more details of cases of carpal tunnel syndrome. The relation between musculoskeletal symptoms reported by 6 months from randomisation and survival from 9 months onwards was assessed by Cox proportional hazards models. The trial is registered, number ISRCTN11883920. It has completed accrual and follow-up is continuing for enrolled participants. FINDINGS: After a median follow-up of 91·0 months (IQR 83·0-99·2), carpal tunnel syndrome had been reported for 66 (2·8%) of 2319 patients in the exemestane group compared with 13 (0·6%) of 2338 in the tamoxifen group (odds ratio [OR] 5·23, 99% CI 2·39-11·49; p

[In search of safety and quality: the improvement model proposed by the Oncology Department of the Palermo University] Over the past 20 years the field of oncology has product therapeutic innovations that have radically changed the prognosis of the most prevalent malignancies, since introduction of so-called targeted molecular agents. As a result of these changes, also the management of cancer patients has become more complex requiring technologies and skills that involve many professionals (medical oncologists, biologists, molecular geneticists, surgeons, pathologists, radiologists, nurses and psychologists), each engaged in a different stage of the disease, with the common goal of ensuring the patient the best treatment available today. So as well as have the chemotherapy changed, have also changed the needs of patients during the execution of the chemotherapeutic program. These changes have affected several areas of therapeutic sphere and in particular the aspect of safety during prescription, preparation, distribution and administration of chemotherapy, and the psychological aspect of the cancer disease, which focused on the acceptance of the disease by using tools such as music, sports, painting and initiatives for the care of the physical appearance (make-up). Not only. The patient wants to be treated today with the guarantee that the proposed protocols are adhering to the most authoritative international guidelines and that staff are highly qualified in the management of all stages of the disease and possible toxicity observed during treatment. Here’s the experience of the Oncology Unit of the University Hospital of Palermo that proposes itself as a leader of a movement to improve the quality of care to offer today to cancer patients in Italy. * Altri coautori: Giuseppe Badalamenti 1, Giuseppe Cicero 1, Fabio Fulfaro 1, Gaetana Rinaldi 1, Sergio Rizzo 1, Antonio Galvano 1, Francesca Lo Vullo 1, Andrea Pasquale 2, Erminia Taormina 2, Dario Piazza 1, Rossella De Luca 1

e14676 Background: HCC accounts for approximately 90% of all primary liver cancers, and is the fifth most common cancer in the world and prognosis is so far very poor,particularly in E patients.Between all tentative of treatment till know SFB seems to be the most promising drug in patients with advanced or metastatic HCC.Aim of the study is to investigate if SFB is efficient and safe also in E HCC patients despite the comorbidities and other problems. Objectives: To investigate if CgA and VEGF work as predicting factors of Sorafenib treatment outcomes. Methods: 51 patients, mean age 68,9 (65-85) with HCC were enrolled . Serum CgA, VEGF and αFP were evaluated at baseline and after end of treatment (SFB 400mg p.o. bid), until disease progression. Clinical response (RECIST), Comprehensive Geriatric Assessment and PFS were considered as well. Results: CgA mean value (baseline: 77.9 – after treatment: 26.25 UI/L) and VEGF levels (baseline: 67.3 – after treatment 47.2 pg/ml) seems to have a predictive role in clinical benefit. A correlation between lower values of CgA and VEGF was noted in pts with longer PFS. Furthermore 3-4 toxicity was not observed in these pts. OS median was 11 months. Conclusions: The most relevant data in this study refer to the role of serum CgA and VEGF levels, for prediction of tumor response. If these findings were confirmed in future largest studies, it could be sufficient to measure these markers levels for identification of those HCC patients who have more probability of obtaining clinical benefit from a sorafenib treatment.

Background: A limit to delivery of cytotoxic chemotherapy in elderly people with cancer, is severe toxicity as principal side effect of treatment. We designed in 2009 a treatment schedule to evaluate E&S of combination of three drugs O, C plus B in ACRC very old patients in a metronomic mode (M-COB) Methods: 75 (37 f -38 m) very elderly patients with advanced colorectal cancer (median age:76; range: 70-82) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to all pts to assess eligibility for chemotherapy. Treatment schedule was: O (65 mg/m2) + B (7.5 mg/Kg) on day 1 (O doses was adjusted by Kintzel-Dorr formula). C (fixed dose of 1,000 mg bid) was delivered from day 2 to day 15 every 3 weeks for 12 cycles. Primary endpoints: toxicity profile (NCI-CTC v2.0) and QoL score (EORTC QLQ-C30). Secondary endpoints:. Clinical Response Rate (CRR) by WHO ‘s criteria. All patients were evaluated for main toxicity (Hemat, G.I., HFS, N&V) by ECOG Common Toxicity Criteria. Results: 76 patients were included into groups I Balducci's classification, for frailty assessement. A 50.1% tumor response rate(TRR) was observed both with a 86.7% Clinical Benefit (CB). No one pts experienced grade 4 toxicity. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 23.5 months with a 12 months survival probability of 78.8%. Conclusions: We choose fixed dose of C in order to reduce main toxicity as shown in std treatment of aged pts with ACRC. Nevertheless this don’t impact on efficacy of treatment. Finally the high rate of clinical benefit encourage further enrollement of patients.In conclusion this schedule seem to be active and safe because improves tolerability without any decrease of efficacy in this kind of patients.

The clinical management of the oncological elderly patient represents one of the most important challenges for today's oncology and, above all, for the future. The number of elderly patients with neoplastic pathologies is destined to increase proportionally to the duration of life and therefore a correct management of their conditions becomes an element of priority from the scientific and economic point of view. Close relationships and collaborations between Oncologist and Geriatrics are definitely desirable to be able to guarantee the best way for a good treatment (specific and of support) of these elderly patients. The components of the AIOM Working Group on Oncogeriatry have gathered their individual competences in the two sectors of specific interest, representing an important form of real cohesion among specialistic disciplines which, after only eight months of activity, has already started to give the first good outcomes.

Background: Older individuals always experience enhanced susceptibility to the side effects of cytotoxic chemotherapy. The aim of the study was to evaluate impact of BEV in combination with OX and XEL in ACRC elderly patients. Methods: 56 (29 male, 27 female) elderly patients with ACRC (median age: 71; range: 66-80) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. The dose of IRI and XEL was adjusted according to Kintzel-Dorr formula. Primary endpoint: clinical response rates (RR) according to WHO criteria. Secondary endpoints: toxicity profile using NCI-CTC v2.0 and quality of life (QoL) score measured through EORTC QLQ-C30 questionnaires. All patients were evaluated for toxicity according to the ECOG Common Toxicity Criteria. BEV adverse reactions were not experienced by any patients. Results: Based on CGA, 48 patients were included into groups I, according to Balducci's classification of frailty and treated with OX (100 mg/m2) + BEV (7.5 mg/Kg) on day 1, and XEL (fixed dose of 1000 mg b.i.d) assumed orally from day 2 to day 15, every 3 weeks for 6 months. None of the pts needed any delay in drugs delivery. Tumor response rates observed were 48% (CR+PR). Clinical benefit, including SD, was 77%. No grade 4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Conclusions: In elderly ACRC patients the dose reduction of XEL through fixed daily dose administration of 1000 mg b.i.d. allows to reach a good tolerability profile with a significant reduction of all grades toxicity compared to dosage calculated according to patients' body surface. We have employed a fixed dose of XEL to obviate the inherent difficulties in dosing with different tablet sizes and to improve compliance with oral chemotherapy assumption in patients with a worse IADL profile. This regimen seems to be active and safe and authors believe that dose reduction improves tolerability without a decrease in efficacy. DFS and OS is under evaluation.

Background: EABC affects about 45% of all advanced breast cancers and actually treatments are always more toxic than effectiveness. Fulvestrant (F), the first of a new class of pure estrogen receptor antagonists, competitively binds to estrogen receptors on tumors and inhibit tumor growth. Capecitabine (C) is converted to 5-FU by thymidine phosphorylase and shows good efficacy and low toxicity as single agent in EABC. Since elderly cancer pts are extremely susceptible in development of rapid toxicity during treatment with cytotoxic drugs, we design this chemo-hormone combined schedule to evaluate if F + C could increase efficacy profile in EABC women. Methods: 41 EABC pts (mean age 72; range 65-88) PD after TAM or SERM were included in the study starting in 2007. Written informed consent for treatment's schedule was acquired from all pts. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. Furthermore the C dose was adjusted according to Cocroft and Kintzel-Dorr formulas. Primary endpoint: clinical response rates (RR) according to WHO criteria. Secondary endpoints: TTP, Toxicity Profile and QoL score measured by NCI-CTC v2.0 and EORTC QLQ-C30 questionnaires. Results: 41/41 pts were evaluated. All pts received C 1,000 mg/m2 b.i.d p.o. on days 1st to 14th every 21 days and F 250 mg i.m. once-monthly until disease progression. Based on CGA all patients were included into groups I-II, according to Balducci's classification of frailty. None of the pts needed any delay in drugs delivery. We observed 13/41 (32%) partial responses and 17/41 (41%) stable disease, for a Clinical benefit of 73%. Median time to progression was 15,6 months. No grade-4 toxicity was experienced. QoL score improvement was appreciated in all pts after end of treatment. Conclusions: Efficacy and Safety results show that this schedule is feasible for EABC pts affected by one or two comorbidities and also in frail condition. All pts are still alive and under monitoring for long-term toxicity and QoL. These results shows that F+C schedule increase clinical benefit-enhancing effectiveness and safety. Although a larger number of EABC pts must be enrolled to consolidate these findings.

Background: ACRC is one of most common neoplastic disease in very old pts. The administration of oral fluoropyrimidine (capecitabine-CAP) in a standard schedule of 1,200 mg/sqm twice a day for 14 d shows similar effects to 5-FU continuous infusion (C.I.). Furthermore, CAP- IRI showed super -additive antitumor activity. Recently many study show the safety and efficacy of a "flat dose" administration of CAP particularly in the treatment of elderly people with cancer. Also, the efficacy of BEV is well demonstrated in CRC pts. Aim of the study is to evaluate impact of bevacizumab (BEV) in combination with IRI and XEL in ACRC very old patients. Methods: 42 (20 f-22 m) elderly patients with advanced colorectal cancer (median age: 77; range: 73-91) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. All Patients were included into groups I, according to Balducci's classification of frailty. Primary endpoint: clinical response rates (RR) according to RECIST criteria and toxicity profile using NCI-CTC v2.0. Secondary endpoints: PFS, OS and QoL score measured through EORTC QLQ-C30 questionnaires. All patients were evaluated for common treatment-related adverse events with regard to haematological and liver toxicity, nausea and vomiting, stomatitis, diarrhea, hand/foot syndrome and sensory neuropathy, according to the ECOG Common Toxicity Criteria. Results: Patients were treated with IRI (180 mg/mq) + BEV (7.5 mg/Kg) on day 1q21, and XEL (fixed dose of 1,000 mg bid) assumed orally continuously for a maximum of 12 cycles. Medium value of cycles delivered was 9.7. Tumor response rates observed were 37.1% (CR+PR). Clinical benefit, including stable disease, was 77.8%. No grade 4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 22 months with a 12 months survival probability of 77.8%. Conclusions: In elderly ACRC BEV plus IRI every 3 weeks with CAP continuously show a good toxicity and effectiveness profile and seem to be a valid terapeutical opportunity also for ACRC very old patients.

This article reviews the principles of systemic cancer treatment in older individuals. These include: assessment of physiologic age with a comprehensive geriatric assessment (CGA), adjustment of chemotherapy doses to the patient's renal function, and prevention of myelotoxicity with hemopoietic growth factors. Other complications that become more common with age include mucositis, peripheral neuropathy and cardiomyopathy. Two chronic complications of chemotherapy become more common with age, including myelodysplasia and chronic cardiomyopathy. The goal of systemic cancer treatment in the older person should include prolongation of active life-expectancy and compression of morbidity in addition to prolongation of survival and symptom management.