Performance of the Multidimensional Geriatric Assessment and Multidimensional Prognostic Index in predicting negative outcomes in older adults with cancer.

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.

Treating cancer in older and oldest old patients.

The so-called "silver tsunami" is a metaphor that the individuals 65 and older represent the most rapidly growing segment of the Western world population. Aging is an ongoing process that leads to the loss of functional reserve of multiple organ systems, increased susceptibility to stress, it is associated with increased prevalence of chronic disease, and functional dependence. Determined by a combination of genetic and environmental factors, this process is highly individualized and poorly reflected in chronologic age. The heterogeneity and the complexity of the older old population represent the main challenge to the treatment of cancer in those patients. We should discern "fit" elderly in whom standard cancer treatment appears to be comparable to a younger population and "unfit" or "frail" elderly, in which the risks of the treatment may overwhelm potential benefits. There are many aspects that have to be assessed before treating an elderly patient, or before to choose the treatment itself. In our review we will try to explain and describe the meaning and the most important aspects related to the oldest old complex patients, and how to manage those patients.

Interventional oncology in the elderly: complications and early response in liver and kidney malignancies.

OBJECTIVES: The complication rate, loco-regional responses and length of hospital stay were analyzed in patients with liver and kidney cancer older than 70years treated with interventional oncology procedures. The findings from the older population were compared with the younger patients (<70years) to detect any difference not related to chance. MATERIALS AND METHODS: Prospectively collected data on patients who underwent hepatic artery embolization (with or without radiofrequency ablation) and kidney radiofrequency ablation were retrospectively analyzed. Complication rates, loco-regional responses and length of hospital stay for patients older and younger than 70 were compared. RESULTS: 163 patients were treated, 66 (40.5%) older and 97 (59.5%) younger than 70years. The complication rate in patients older than 70 was 4.5% (3/66 pts) versus 3.1% (3/97 pts) (p=0.69) in the younger age-group. The complication rates for the liver embolization group, liver embolization plus radiofrequency and kidney radiofrequency group were 2/90 pts (2.2%), 2/42 pts (4.8%) and 2/31 pts (6.5%), respectively (p=0.46). Median hospital stay was three nights in both older and younger patients. Response rates were not significantly influenced by age. CONCLUSION: Liver embolization with or without radiofrequency and renal radiofrequency are safe and effective in older patients. Age alone should not be considered a contraindication to treatment in carefully selected patients.

Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper.

BACKGROUND: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin's lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered. METHODS: A committee of experts in breast cancer and NHL met under the auspices of the International Society for Geriatric Oncology to review the literature and make recommendations, based on level of evidence, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines. RESULTS AND RECOMMENDATIONS: Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening for risk factors, rigorous monitoring of cardiac function and early intervention. Use of liposomal anthracycline formulations, prolonging the infusion time for conventional anthracyclines and cardioprotective measures should be considered. However, when treatment is being given with curative intent, care should be taken to ensure reduced cardiotoxicity is not achieved at the expense of efficacy.

EORTC elderly task force position paper: approach to the older cancer patient.

As a result of an increasing life expectancy, the incidence of cancer cases diagnosed in the older population is rising. Indeed, cancer incidence is 11-fold higher in persons over the age of 65 than in younger ones. Despite this high incidence of cancer in older patients, solid data regarding the most appropriate approach and best treatment for older cancer patients are still lacking, mostly due to under-representation of these patients in prospective clinical trials. The clinical behaviour of common malignant diseases, e.g. breast, ovarian and lung cancers, lymphomas and acute leukaemias, may be different in older patients because of intrinsic variation of the neoplastic cells and the ability of the tumour host to support neoplastic growth. The decision to treat or not these patients should be based on patients' functional age rather than the chronological age. Assessment of patients' functional age includes the evaluation of health, functional status, nutrition, cognition and the psychosocial and economic context. The purpose of this paper is to focus on the influence of age on cancer presentation and cancer management in older cancer patients and to provide suggestions on clinical trial development and methodology in this population.

Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years) women with metastatic breast cancer? Early interruption of a phase II study.

BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer with moderate toxicity, in 2002 we started a phase II trial with a combination regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with advanced breast cancer and measurable lesions. All patients underwent multidimensional geriatric assessment before enrollment. A two-step design was applied, and the trial would be completed if an overall response rate>or=30% was obtained with a grade 3-grade 4 (G3-G4) toxicity rateor=70 years outside the setting of controlled clinical trials.

Is acute dyspnea related to oxaliplatin administration?

The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin. Oxaliplatin improves the efficacy of this combination in patients with stage III colon cancer and moreover its toxicity is well tolerable. We describe a rare clinical case of acute dyspnoea probably related to oxaliplatin at one month from the end of the adjuvant treatment. A 74-year-old man developed a locally advanced sigmoid carcinoma (pT3N1M0). A port a cath attached to an open-ended catheter was implanted in order to administer primary chemotherapy safely according to the FOLFOX4 schedule. One month following the end of the 6th cycle, the patient referred a persistent cough and moderate dyspnoea. Chest radiography displayed a change in the lung interstitium, chest CT scan confirmed this aspect of adult respiratory distress syndrome, spirometry reported a decreased carbon monoxide diffusion capacity. Antibiotic and corticosteroids were administered for 10 d, then a repeated chest X ray evidenced a progressive pulmonary infiltration. A transbronchial biopsy and cytology did not show an infective process, a CT scan reported radiological abnormalities including linear and nodular densities which were becoming confluents. Antimicotic and antiviral drugs did not evidence any benefit. The antiviral therapy was stopped and high dose metilprednisolone was started. The patient died of pulmonary distress after 10 d.

Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer.

The primary objective of study is to evaluate cardiac safety of trastuzumab in combination with epirubicin and docetaxel. HER2-overexpressing metastatic breast cancer patients were enrolled in a two-stage, multicenter phase II trial with weekly trastuzumab (4 and then 2 mg/kg) with epirubicin and docetaxel (either 75 mg/m(2)) on day 1 every 3 weeks. After eight courses of chemotherapy, trastuzumab was continued as a single agent. To assess cardiotoxicity, patients were evaluated for left ventricular ejection fraction (LVEF) at baseline, every two cycles during chemotherapy and trastuzumab, and every 3 months during trastuzumab alone. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure (CHF) and/or an absolute decrease in LVEF of >or=20 units or a decline to

A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer.

BACKGROUND: Oxaliplatin (OXA) significantly enhanced the antitumour activity of 5-fluorouracil (FUra) in patients with advanced colorectal cancer and displayed radiosensitising properties in preclinical studies. This study was thus performed to test the feasibility, identify the recommended doses (RDs) and explore preliminarily the clinical activity of weekly OXA and infused FUra combined with preoperative pelvic radiotherapy. PATIENTS AND METHODS: Forty-six patients with recurrent or locally advanced (cT3-4 and/or N+) adenocarcinomas of the mid-low rectum were treated with escalating doses of OXA (25, 35, 45, 60 mg/m2, weekly for 6 weeks) and FUra (200-225 mg/m2/day, 6-week infusion) concurrent to preoperative pelvic radiotherapy (50.4 Gy/28 fractions). The RDs for the phase II part of the study were immediately below the level resulting in dose-limiting toxicities in more than one third of the patients, or corresponded to the last planned dose level. RESULTS: In the escalation phase, dose-limiting toxicities only occurred in one patient at the fourth level and one of six patients treated at the last planned dose level (grade III diarrhoea). OXA 60 mg/m2 and FUra 225 mg/m2/day are therefore the RDs for the regimen. Among 25 patients globally treated at these doses (phase II part), the incidence of grade III diarrhoea was 16% with no grade IV toxicity. Neurotoxicity did not exceed grade II (12%). All patients completed radiotherapy and were operated on as scheduled. Twenty-one of 25 patients had the tumour down-staged after chemoradiation with seven (28%) pathological complete responses and 12 (48%) residual tumours limited to ypT1-2N0. CONCLUSIONS: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.

Adjuvant chemotherapy for elderly patients (> or =70 years) with early high-risk breast cancer: a retrospective analysis of 260 patients.

BACKGROUND: Adjuvant chemotherapy in elderly women is currently perceived as one of the priorities in breast cancer (BC) research and, to date, we lack practical guidelines in this age group. Therefore we performed a retrospective analysis of the actual use of adjuvant chemotherapy according to each negative prognostic factor. PATIENTS AND METHODS: Charts of all consecutive elderly patients aged 70 years or more with operable BC referred to our institution between 1999 and 2003 were reviewed for tumour stage and treatment, and compared with an equal cohort of younger randomly selected postmenopausal patients (control group). RESULTS: A total of 260 elderly patients (mean age 75.6 years, age range 70-97 years) with histological diagnosis of early BC were eligible. Conserving surgery was performed in 54.6% of patients, nodal dissection in 84.6% and sentinel node biopsy in 5.8%. Tumour size was pT2-pT3 in 45.4% of patients; grading was G3 in 27.3%, hormonal status was negative (HR-) in 16.9% and lymph nodes were involved N+ in 36.1%. Of 188 patients presenting one or more risk factors (pT2-3, G3, N+, HR-), 48.4% were not proposed for adjuvant chemotherapy (compared with 7.2% in the control group), 39.8% of those with nodal involvement (compared with 4.3% of controls, P <0.0001) and 22.7% of those who were HR- (compared with 0.0% of controls, P=0.0002). Considering only patients receiving non-anthracycline-based chemotherapy, 20 elderly patients (25.9%) were unable to complete the planned number of cycles (compared with 4.7% of controls, P=0.0002). The 2-year disease-free survival was significantly decreased in N+ HR- patients compared with the remaining elderly patients (49.9% compared with 90.9%, P=0.0006). CONCLUSIONS: Elderly BC patients receive much less adjuvant chemotherapy, according to each prognostic factor. N+ HR- disease probably represents the most reasonable indication. As the toxicity of the CMF regimen frequently caused interruption of treatment, alternative regimens should be assessed in this age class.

Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas.

BACKGROUND: Frail patients with non-Hodgkin's lymphoma (NHL) are generally excluded from clinical trials and not even treated. The aim of this study was to evaluate the efficacy and tolerability of vinorelbine and prednisone in frail elderly patients with NHL. PATIENTS AND METHODS: Thirty consecutive frail elderly patients were entered in a phase II study with vinorelbine 25 mg/m2 i.v. on days 1 and 8 and oral prednisone 30 mg total dose on days 1-8 for six cycles. Criteria of frailty were age > or =80 years, or age > or =70 years and three or more comorbidities of grade 3 or at least one comorbidity of grade 4 according to the Cumulative Illness Rating Scale (CIRS), or not self-sufficient or the presence of one or more geriatric syndromes. RESULTS: Of 30 evaluable patients, three (10.0%) achieved a complete response (CR), nine (30.0%) showed a partial response (PR), while 10 presented with stable disease and eight with progressive disease. The median duration of CR was 29 months (range 5-36 months), and the median duration of PR was 1 month (range 1-22 months). Three patients had grade 3 neutropenia and one had grade 4. One grade 4 neurotoxicity was observed. Three patients died because of heart failure within 28 days of therapy, and one patient died after 4 days because of rapid progression. The median overall survival was only 10 months. CONCLUSION: Vinorelbine and prednisone is a relatively non-toxic combination with modest activity in frail patients with NHL. If initial aggressive chemotherapy has been excluded, this combination could be tried to obtain a temporary palliation.

Multidimensional geriatric evaluation in elderly cancer patients: a practical approach.

Management of cancer in the elderly population is currently perceived as one of the major challenges for clinical research in medical oncology. Multidisciplinary evaluation of the malignant disease and multidimensional assessment of the host represent the key element for correct decision making. Standard methods developed by pioneer geriatric oncologists will be summarized in this review, along with some practical suggestions on when and how they should be employed. Future perspectives concerning some critical issues in multidimensional geriatric assessment will be discussed as well.

RFS2000 (9-nitrocamptothecin) in advanced small cell lung cancer, a phase II study of the EORTC New Drug Development Group.

Camptothecins have shown efficacy in terms of response rate in patients with small cell lung cancer (SCLC). RFS2000 is a new camptothecin derivative, which has shown objective responses in various tumour types. The aim of this phase II study was to determine the objective response rate of RFS2000 in patients with sensitive and refractory SCLC. RFS2000 was given orally at 1.5 mg/m(2) per day for five consecutive days (five days on - two days off) on a continuous basis. Patients were evaluated weekly for toxicity and every six weeks for response. Thirty seven patients were included, 36 patients (14 with sensitive and 22 with refractory SCLC) were evaluable for toxicity, and 35 patients were evaluable for response. No objective responses were observed. Toxicity was acceptable, with myelosuppression, nausea/vomiting, and diarrhoea as the main toxicities. RFS2000 therefore has an acceptable toxicity profile but is not active as a single agent in SCLC.