Management of Frail and Not-Frail elderly cancer patients in a hospital-based geriatric oncology program.

PURPOSE: To evaluate management and outcome of patients >or=70 years admitted to our Medical Oncology ward and evaluated by Multidimensional Geriatric Assessment before treatment with standard or "elderly-friendly" chemotherapy regimens, a list of which was developed within our Geriatric Oncology Program based on published clinical trials and personal experience. PATIENTS AND METHODS: Charts of patients treated from January 2004 to January 2006 were reviewed for choice of treatment, tumor response, toxicities and survival. RESULTS: 117 patients (median age 75 years) were divided into Frail (F) (34.2%) and Not-Frail patients (NF: 33.3% Fit plus 32.5% Vulnerable). The two groups did not differ according to the use of "elderly-friendly"chemotherapy regimens (40% of F pts and 39% of NF pts), dose reductions >or=25% (37.5% vs. 31.2%) and grade 3-4 toxicities (52.5% vs. 58.4%). Early interruption of treatment due to toxicity or patient's refusal (42.5 vs. 15.6, p=0.001) and deaths within 30 days from last chemotherapy administration (22.5% vs. 3.9%, p=0.003) were significantly different. F patients showed clinical or radiological response in 21.2% of cases, and subjective improvement in 22.6%. After a median follow-up of 19 months, median survival of F patients (6.4 months) is shorter compared to NF group (16.9 months, p=0.012). CONCLUSIONS: The use of "elderly-friendly"chemotherapy regimens was limited to less than a half of cases. F patients may respond to chemotherapy but display higher rates of premature withdrawal and early deaths compared to NF patients, with a shorter survival. Clinical trials particularly aimed at frail patients are urgently needed.

Oral anticancer drugs in the elderly: an overview.

The increasing number of elderly people in the world population has led to a parallel increase in the number of older cancer patients, with over 45% of all cancers in Europe occurring in patients >70 years of age. The increasing tendency to use oral chemotherapy is thus of interest in the elderly, given that both elderly patients and their physicians prefer to use less complex and toxic regimens when such treatments have equivalent efficacy to more complex regimens. However, data from studies designed to evaluate these therapies in the elderly are currently limited. Factors that must be considered before prescribing oral agents to this subset of patients include age-related physiological changes affecting clinical pharmacology, adherence, the patient's capability to self-administer medications, and safety issues concerning the older patient and his or her caregivers. The idea that elderly patients may benefit from the introduction of oral chemotherapy is very fashionable, but to date there is no proof that this approach is as effective as intravenous therapy in this age group, particularly since randomised trials are lacking. This review discusses these issues and reviews current information about the use of specific oral chemotherapeutic drugs for major neoplastic diseases in the elderly.

Ifosfamide-related encephalopathy in elderly patients : report of five cases and review of the literature.

Encephalopathy is a serious adverse reaction occurring in 15-30% of patients treated with the alkylating agent ifosfamide. Patients with this adverse effect may experience seizures, drowsiness, confusion and hallucinations of different grades of severity. In this article, we describe five cases of acute CNS toxicity in patients aged > or =65 years of age treated with ifosfamide and we review data on the management and outcome of this serious complication in elderly patients. All five patients experienced symptoms of encephalopathy soon after receiving combination chemotherapy including ifosfamide for different tumours. All of the patients had been assessed by means of a Comprehensive Geriatric Assessment for the presence of associated diseases, disability, cognitive status and depression, and scores were satisfactory in all patients, although case 5 was deemed frail because of cancer-related limitation in movement. In four patients, the antidote methylene blue (methylthioninium chloride) was administered intravenously, with successful recovery in three patients and a fatal outcome in the fourth patient. The fifth patient rapidly recovered after discontinuation of ifosfamide and did not receive methylene blue. The roles of older age, peak ifosfamide concentration, low albumin levels, increased serum creatinine and bulky abdominal disease as predisposing factors for ifosfamide-related encephalopathy in retrospective series are controversial.Although methylene blue has been frequently administered in patients with ifosfamide-related encephalopathy, its efficacy in this context has not been assessed objectively. Thus, careful baseline evaluation of elderly patients and constant clinical observation during infusion, especially during the first course of therapy, are recommended to reduce the risk of severe CNS toxicity from ifosfamide.

Platinum-etoposide chemotherapy in elderly patients with small-cell lung cancer: results of a randomized multicenter phase II study assessing attenuated-dose or full-dose with lenograstim prophylaxis--a Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP-GSTPV) study.

PURPOSE: Small-cell lung cancer (SCLC) is increasingly diagnosed in elderly patients, who are at higher risk of treatment-related morbidity and mortality. We conducted a randomized two-stage phase II study to assess the therapeutic index of two different platinum/etoposide regimens, attenuated-dose (AD) and full-dose (FD) plus prophylactic lenograstim. PATIENTS AND METHODS: SCLC patients older than 70 years were randomized to receive four courses of cisplatin 25 mg/m(2) on days 1 and 2, and etoposide 60 mg/m(2) on days 1, 2, and 3 every 3 weeks (AD); or cisplatin 40 mg/m(2) on days 1 and 2, and etoposide 100 mg/m(2) on days 1, 2, and 3 every 3 weeks, plus lenograstim 5 mg/kg days 5 through 12, every 3 weeks (FD). A combined primary end point named therapeutic success (TS), which took into account activity, toxicity, and compliance, was used. RESULTS: Ninety-five patients were enrolled. Seventy-five percent and 72% of the patients in the AD and FD arms, respectively, completed the treatment as per protocol. Response rate was 39% and 69% in the AD and FD arms, respectively, and 1-year survival probability was 18% and 39%, respectively. Treatment was well tolerated in both groups, with no grade 3 to 4 myelotoxicity in the AD arm, and 12% myelotoxicity in the FD arm. Overall, the observed TSs were 10 (36%) of 28 patients and 42 (63%) of 67 patients for AD and FD treatments, respectively. CONCLUSION: In elderly patients with SCLC a full-dose cisplatin/etoposide regimen combined with prophylactic lenograstim is active and feasible, while attenuated doses of the same regimen are associated with a poor therapeutic outcome.

Old and new drugs in systemic therapy of pancreatic cancer.

BACKGROUND: The incidence of pancreatic cancer nearly equals its death rate (97%). Two-year survival is about 10%. Chemotherapy treatment is problematic because of the palliative and limited duration of response. MATERIAL AND METHODS: The article analyzes the objective response and median survival time (MST) for old and new drugs in the treatment of pancreatic cancer. RESULTS: The most encouraging results to date come from studies of 5-fluorouracil (5FU) as an adjuvant therapy and of gemcitabine in the advanced disease, which is one of the most active and best tolerated drugs in recent years. However, with the introduction of new drugs or with different old drug associations, interesting results are also becoming evident. CONCLUSIONS: New approaches to CT treatment are necessary. Patient enrollment into rigorous and well conducted clinical trials, either at tumor diagnosis or after tumor recurrence, will generate new information regarding investigational therapies and it will offer improved therapies for patients with this disease.

Is there a role for chemoradiotherapy in the treatment of pancreatic carcinoma?

Pancreatic adenocarcinoma is the fifth leading cause of cancer-related death in the United States. In spite of advancements in surgical treatments, nearly 80% of patients with localised pancreatic cancer die of recurrent or metastatic disease when treated with surgery alone. Therefore, efforts to alter the patterns of recurrences and improve survival for patients with pancreatic cancer currently focus on the delivery of systemic therapy and irradiation before or after surgery. Postoperative adjuvant therapy appears to improve median survival. Utilizing a preoperative approach, overall treatment time is reduced, a greater proportion of patients receive all components of the therapy and patients with rapidly progressive disease are spared the side-effects of surgery. This paper examines the factors pertinent to clinical trial design for pancreatic cancer and reviews the existing data supporting adjuvant and neoadjuvant therapy for potentially resectable disease and chemoradiotherapy in the advanced disease.

[Therapeutic decision in medical oncology]. / La decisione terapeutica in oncologia medica.

The clinical decision in medical oncology is difficult to take. To develop a decisional system based on evidence based medicine, guidelines and protocols could be useful in many complex situations.

Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study.

BACKGROUND: Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated. METHODS: Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration-time curve 5 on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8, and 15. This cycle was repeated every 4 weeks. RESULTS: Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0-1, 56% had Stage I-II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m(2) per week, which was 82% of the planned dose (750 mg/m(2) per week). For carboplatin, the delivered dose intensity was 80 mg/m(2) per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty-six percent of the patients had partial responses (95% confidence interval: 15-40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13-113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3-4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3-4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3-4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression-free survival period was 40 weeks. CONCLUSIONS: The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3-week cycles instead of 4-week cycles) would permit a more optimal treatment administration.