The impact of new cancer drugs in real practice oncology: a monoinstitutional experience.

Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (e.g. value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. We have analyzed a total of 856 cancer patients were registered in the onco-AIFA for various drugs. The results have shown that 38.1% of patients have received only few drug administrations and their treatment was stopped within 4 or 12 weeks (depending on the type of the drug schedule). We have examined the reasons, why their treatment was immediately suspended.

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study.

Recent studies have reported the potential clinical utility for metastatic breast cancer (MBC) patients of continuing trastuzumab beyond progression. Based on those results, here the authors have examined the benefits of trastuzumab-continuation by specifically evaluating RECIST responses upon first line trastuzumab-treatment as a potential predictive marker for therapeutic effect of trastuzumab-continuation beyond metastatic disease progression. The authors carried out a retrospective analysis of 272 HER2 positive MBC patients under trastuzumab treatment at 22 different oncology Italian centers during the years of 2000 and 2001 who progressed under first line trastuzumab-treatment. The primary end point of the study was the survival from the date of first documented progression upon first line trastuzumab treatment of disease. Data analysis involved the use of matching on propensity score to balance variables between treated and untreated subjects and to reduce bias. Of the 272 HER2-positive MBC patients, 154 (56.6%) continued treatment. 79 (51.3%) of those 154 patients showed responses based on RECIST criteria during first-line trastuzumab-treatment. Of the 118 patients that suspended trastuzumab, RECIST responses had been observed in 44 (37.3%). Cox proportional hazards analysis of progressed patients, matched using propensity score, showed that discontinuation of trastuzumab at metastatic disease progression was a risk factor for significantly reduced overall survival in both responder (HR = 2.23; 95% CI = 1.03-4.82) and non-responder groups (HR = 3.53, 95% CI = 1.73-7.21), with no significant differences in the two estimated HRs (P-value of the likelihood-ratio test = 0.690). Continued trastuzumab treatment after disease progression has clinically and statistically significant effects in both RECIST responder and non-responder MBC patients.

When an interim analysis of randomized trial changes the practice in oncology: The lesson of adjuvant trastuzumab and the HERA trial.

About 30% of the randomized clinical trials are stopped early because of appearance of clear clinical benefit. Though interim analyses protect patients in case of significant imbalance between two treatment arms, conclusions drawn from truncated studies can be premature and should be viewed with caution. We report the lesson learnt from the Herceptin adjuvant (HERA) trial.

When an interim analysis of randomized trial changes the practice in oncology: the lesson of adjuvant Trastuzumab and the HERA trial.

About 30% of the randomized clinical trials are stopped early because of appearance of clear clinical benefit. Though interim analyses protect patients in case of significant imbalance between two treatment arms, conclusions drawn from truncated studies can be premature and should be viewed with caution. We report the lesson learnt from the Herceptin adjuvant (HERA) trial.

Neoadjuvant carboplatin and vinorelbine followed by chemoradiotherapy in locally advanced head and neck or oesophageal squamous cell carcinoma: a phase II study in elderly patients or patients with poor performance status.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of neo-adjuvant carboplatin and vinorelbine followed by concomitant chemoradiotherapy in patients > or =70 years of age or with Karnofsky performance status (PS) 70-80, diagnosed with locally advanced head and neck (H&N) or oesophageal carcinoma. PATIENTS AND METHODS: The treatment plan consisted of three courses of carboplatin AUC4 on day 1 and vinorelbine 25 mg/m2 on day 1 and 8, every 21 days, followed by chemoradiotherapy. Carboplatin 100 mg/m2 was delivered weekly for the duration of the radiation therapy (70 Gy, 2 Gy/daily). RESULTS: Thirty-five patients with an average age of 68 years (range 42-85, 16 patients > or =70 years) were treated. Twenty-seven patients (77.1%) responded to neo-adjuvant chemotherapy (2 complete and 25 partial responses). Haematological toxicity was grade 3-4 in 13 patients (37.2%), while gastrointestinal toxicity was grade 3-4 in 20 patients (57.1%). All the patients completed the chemoradiotherapy plan, with grade 4 mucositis plus febrile neutropenia in 3 patients (8.5%). Median time to progression (TTP) was 10.2 months, with 31.5% of patients being alive at two years. CONCLUSION: The regimen of neo-adjuvant carboplatin and vinorelbine followed by chemoradiotherapy is feasible and active in older (> or =70 years) or low PS (Karnofsky 70-80) patients, although toxicity is not negligible and long-term outcome remains poor.

Adjuvant systemic chemotherapy with 5-fluorouracil and leucovorin in colon cancer: a monoinstitutional institutional experience.

The efficacy of adjuvant chemotherapy in colon cancer has been well established in clinical trials, yet data on its routinely clinical practice are few. Two hundred forty-one patients were treated with fluorouracil-based adjuvant therapy from 1996 to 2001 and 147 out of 241 patients consecutively treated was aged 65 years or more at the time of diagnosis. Kaplan-Meyer progression-free survival and overall survival of stage II and III patients were calculated, the same statistic analyses were done for elderly population. Three- and 5-year overall survivals were respectively 94.4% and 90.4%. The survival observed in our retrospective study reflects that reported in the chemotherapy arm of randomized clinical trials. As expected, stage II patients survival was better than that of stage III patients (p = 0.0019, log-rank test). The treatment was generally well tolerated and there was no therapy related death and no clinical immonotoxicological effects was observed also in elderly patients.

Stable disease in advanced colorectal cancer: therapeutic implications.

Colorectal cancer is one of the most common neoplasms in Western Countries and ranks second as a cause of death due to cancer. The overall mortality at 5 years is about 40%. Patients with resectable metastatic disease can be cured, but for those who cannot, treatment is purely palliative, and overall survival (OS) is from approximately 7 to 24 months. Infusional regimen with modulated 5Fluorouracil (5FU) gives an objective response rate (RR) of up to 30-40%. The addition of CPT11 or oxaliplatin to 5FU improves RR, time to progression (TTP) and OS with a stabilization of disease (SD) in 40-70% of cases and 20-40%, respectively. The concurrent utilization of selective biological agents as growth factor receptors acting at a molecular level and influencing the processes of tumor formation and growth, increases tumor cell apoptosis and inhibits tumor growth; as a result, the tumor regresses or is inhibited, with consequently prolonged OS and TTP. This paper examines the problem related to the treatment of metastatic colorectal cancer with SD. Current doubts regarding the continuation of one treatment until disease progression (PD) with a risk of toxicity, whether or not to use a less toxic "maintenance" therapy after a fairly aggressive "induction" therapy in "stabilized" responders, or whether to stop the treatment in the presence of a SD confirmed after at least two consecutive evaluations, are present.

FOLFOX4 in advanced colorectal cancer: a monoinstitutional experience.

AIMS AND BACKGROUND: Patients included in clinical trials are "selected", and they usually differ from those commonly treated. METHODS: From 1999 to 2004, in the Medical Oncology Department of Padua (Italy), 70 metastatic colorectal cancers were treated with FOLFOX4. RESULTS: Our results, compared with those of the registration trial (response rate, duration of response and progression-free survival) appeared lower; overall survival was improved. CONCLUSIONS: The number of therapeutic regimens more than their type influenced the results.

Colorectal cancer adjuvant treatment in elderly patients.

Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. In Europe, 40% of patients with this disease is over 70 years old and only 52% of them with positive nodes usually receive an adjuvant chemotherapy. Despite early reports to the contrary, these patients tolerate cancer treatment and surgical resections as well as their younger counterparts but as a result of exclusion criteria, those receiving an adjuvant therapy are very few. This paper examines the factors pertinent to the small number of clinical trials designed for adjuvant colorectal cancer in the elderly.

FOLFOX versus FOLFIRI: a comparison of regimens in the treatment of colorectal cancer metastases.

Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the Western world. Already at the time of the primary tumor, 15-25% of the patients present with liver metastases while another 20% will develop metastasis following treatment of the colorectal primary. Without any treatment the median survival after the detection of metastases is approximately 9 months, depending on the extent of the disease at the time of diagnosis. Clinical trials with the "FOLFOX and FOLFIRI families" of drugs, designed for the treatment of metastatic colorectal cancer, their results and the costs of each therapy are examined. For each drug, the cost/mg, the cost/mg/m2 and the cost/therapy (according to its duration) are evaluated according to the prices reported in the Italian Directory of Medicines and Manufacturers, 63rd Edition, November 2003.

Complete remission of poorly differentiated squamous liver carcinoma after systemic chemotherapy and surgery. A case report.

We report the case of a 64-year-old male patient diagnosed as having inoperable poorly differentiated liver carcinoma that could be completely resected after systemic chemotherapy with cisplatin and 5-fluorouracil.

[Questionable methods in cancer therapy]. / Le terapie non convenzionali in oncologia.

Although alternative and complementary therapies are a well known, spread reality, and many alternative cancer cure were generally found ineffective in clinical trials, oncologists don't care of them. While some therapies, such as spiritual healing and relaxation, are low risk if they don't delay effective conventional methods, herbal remedies showed potential adverse reactions. Oncologists should be aware of these products and question patients on their use of them.

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.

Green oncology: cultivating sustainability in medical oncology.

INTRODUCTION: Green oncology is a new conceptual and operational paradigm of oncology, which compared to the traditional biomedical model focused on the interest of a single patient and on its exclusive relationship with the doctor, represents a complex evolutionary step towards clinical activities that have to be eco-responsible of the potential current and future impact on the human, professional, structural, technological, and organizational environment, where they arise, as well as on the biosphere. DEFINITION: Green oncology works through ethical and managerial choices that incorporate, besides the traditional criteria of efficiency and effectiveness, the criterion of cultural, economic, environmental, and social sustainability as they are fair, livable, and possible to be realized.

Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors and new therapeutic perspectives in non small cell lung cancer.

EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of MET, another tyrosine kinase receptor, has been implicated in neoplastic invasive growth. MET is overexpressed, activated and sometimes mutated in NSCLC cell lines and tumor tissues. MET increased gene copy number has also been documented in NSCLC and has been studied as negative prognostic factor. It has also been found in about 20% of patients developing acquired resistance to TKIs inhibitors. In this group, it seems to display a new mechanism, which is able to mark tumor independence from EGFR signaling. The study of delayed resistance mechanisms could lead to the development of new therapeutic strategies. Different molecular alterations could be specifically targeted in order to extend disease control in this group of NSCLCs with distinct clinical and molecular features. EGFR irreversible inhibitors, MET inhibitors and dual EGFR/VEGFR inhibitors represent one of the most challenging issues in current clinical research. Ongoing clinical trials and future perspectives are discussed.

Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience.

BACKGROUND: The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients. METHODS: Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan. RESULTS: Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%). CONCLUSION: Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

Neurological syndrome after R-CHOP chemotherapy for a non-Hodgkin lymphoma: what is the diagnosis?

A 63-year-old man was admitted to our Oncology department for management of a follicular non-Hodgkin lymphoma, stage IV A FLIPI 5. The patient entered chemotherapy following the R-CHOP schedule, and a PET scan after three cycles showed partial remission. One week later he was admitted to our hospital after developing serious pain in his left arm resulting in an impaired function, right facial hemiplegia, and ophthalmoplegia. Neuroimaging studies and laboratory features were negative. Given his symptoms, we suspected Miller Fisher syndrome and the patient was administered high dose immunoglobulin, but showed no improvement. Finally, chemotherapy with methotrexate 3 g/mq was initiated, but his condition progressively worsened and the patient died 2 months later. We suggest that any patient with neurological symptoms who has received rituximab should undergo PCR analysis for all neurotropic viruses together with neurophysiological and neuroimaging studies.