Differences in the availability of new anti-cancer drugs for Italian patients treated in different regions. Results of analysis conducted by the Italian Society Of Medical Oncology (AIOM).

AIMS AND BACKGROUND: Italy is divided into 20 regions. As a consequence of local autonomy, following marketing authorization by the Italian Medicines Agency, each drug for hospital use is not immediately available, because its approval needs to undergo further steps that can be different among regions. The Italian Society of Medical Oncology conducted the present study to describe the impact of the existence of sub-national pharmaceutical formularies on the disparity of access to new anti-cancer drugs among patients treated in different Italian regions. METHODS: The availability of 8 new anti-cancer drugs at a regional level and the coherence of regional authorizations compared with national authorizations approved by the Italian Medicines Agency were analyzed as of April 2009. RESULTS: Fourteen regions and autonomous province of Trento have a regional pharmaceutical formulary. In most cases, the regional pharmaceutical formularies include the eight analyzed drugs, with therapeutic indications coherent with national marketing authorization indications. Five drugs (bevacizumab, trastuzumab, rituximab, erlotinib, sunitinib) were included in all the existing regional pharmaceutical formularies, without restrictions, whereas three drugs (cetuximab, sorafenib, pemetrexed) were found to have restrictions in some regions. CONCLUSIONS: The presence of multiple hierarchical levels of drug evaluation creates a potential element of disparity in the access to pharmacological therapies for Italian citizens.

Gastrointestinal stromal tumors: report of an audit and review of the literature.

Gastrointestinal stromal tumors (GISTs), tumors characterized by c-KIT mutations, are the most frequent mesenchymal tumors of the digestive tract. The stomach is the most commonly involved site. Localization, size and mitotic rate are reliable predictors of survival and the two milestones of GISTs treatment are surgery and imatinib. This article is aimed to report the data of an audit, carried out on the morphological and clinical aspects of the disease and to review the present knowledge on GISTs. A total of 172 patients with GISTs (M : F=1 : 1; mean age 65 years) were recruited. The stomach was the most frequently involved site. In 50% of the cases the tumor was smaller than 5 cm, whereas major symptoms were observed in 43% of the cases. Predictors of progressive disease were present only in a small percentage of cases but the disease was in the metastatic phase in over 25% of the cases at diagnosis. Familial aggregation was rare but a consistent share of the patients (21%) had other synchronous or metachronous cancers. The most frequent mutations were in-frame deletions and point mutations of c-KIT exon 11. This report confirms in part the available data on GIST in a consecutive series of patients recruited in Italy and shows that only large collaborative multicenter studies provide data sound enough to enable making reasonable clinical and therapeutic choices, and suggests that, as a measure of secondary prevention, a diagnostic definition should be obtained in all submucosal lesions of the GI tract and that GIST patients should be screened for second tumors.

Treatment of breast cancer in older women.

BACKGROUND: Breast carcinoma management in the elderly often differs from the management in younger women and there is considerable controversy about what constitutes appropriate cancer care for older women. This controversy is reflected in the persistence of age-dependent variations in care over time, with older women being less likely to receive definitive care for breast cancer. There has been a significant increase in the last years in the number of studies conducted in older patients with breast cancer. Although available age-specific clinical trials data demonstrate that treatment efficacy is not modified by age, this evidence is limited by the lack of inclusion of substantial numbers of older women, particularly those of advanced age and those with comorbidities. METHOD: The literature-based evidence of the last 10 years was extensively reviewed on the main issues concerning the treatment of breast cancer in older women. RESULTS: Surgical treatment in older patients has evolved from avoidance to mastectomy to breast-conserving surgery, similarly to younger patients. Given its negative effect on the quality of life, in the last few years the role of adjuvant radiotherapy has been questioned in elderly patients with breast cancer. Adjuvant chemotherapy benefit in older patients applies mainly to Estrogen-receptor-negative patients, while in Estrogen-receptor-positive patients a major role is played by endocrine treatment. New "elderly-friendly" drugs, that can help clinicians to reduce toxicity, are now available for breast cancer.

Insight into the treatment of cancer in older patients: developments in the last decade.

In the last decades there has been an increased interest in the treatment of elderly cancer patients and a change in attitude of both clinicians and their patients has occurred. Drugs are now available that might be considered "elderly-friendly" and the enormous advances in surgical procedures and supportive treatments over the recent years have enabled adverse effects to be minimized. A Geriatric Assessment is increasingly used as a tool to define those patients who are more suitable for aggressive chemotherapy or, on the contrary, palliative treatment. For almost all cancers, older patients are better treated today than they were in the past, even though we are still far from optimal management. Despite the perceived barriers to including elderly patients in clinical trials, there are few data to support excluding them. We must not permit increased age in cancer patients to continue to be an important and independent risk factor for receiving inadequate care.

Treatments of AIDS-related Kaposi's sarcoma.

Although Kaposi's sarcoma (KS) has decreased in countries where the highly active antiretroviral therapy (HAART) regimen is available, however it remains, after non-Hodgkin's lymphomas, the most common malignancy in HIV+ patients. Advances in the treatment of AIDS-KS have been achieved, even though a gold standard therapy has not been yet defined. With the availability of HAART, a dramatic KS clinical response has been documented, making HAART essential in all patients. In case of aggressive and/or life threatening KS, more complex therapeutic schedules have to be taken into account, including chemotherapy and/or immunotherapy. Liposomal anthracyclines and paclitaxel have been approved by FDA as first line and second line mono-therapy, respectively. Interferon-alpha (INF-alpha) is the only immunomodulant agent to have shown a therapeutic effect. Among the new drugs, many antiangiogenetic agents have produced encouraging responses. Finally, the identification of the HHV-8 as a causative agent and new metalloproteinase inhibitors may offer promising targets for the KS treatment.

Stanford V regimen plus consolidative radiotherapy is an effective therapeutic program for bulky or advanced-stage Hodgkin's disease.

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin's disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease > or =3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%. There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin's disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

A consensus protocol: Image-improved therapeutic guidelines for limited adult Hodgkin's disease.

Hodgkin's disease (HD) has greatly benefited from new technologies in terms of less invasive and more accurate staging as well as improved overall and relapse-free survival. However, the likelihood of late adverse effects of treatment, including second tumors, has increased due to the longer survival of patients with HD. Today's trend is to aim at minimal therapeutic exposure while guaranteeing lower therapy-related morbidity. This encourages new research efforts but also leads to less uniformity in treatments, as observed in the Veneto Region in Italy. The Gruppo Veneto Linfomi, composed of representatives of Radiotherapy and Oncology Departments of the Veneto Region, has been analyzing this problem and proposing therapy guidelines since 1995. A set of 10 prognostic factors has been developed to identify three prognostic groups: highly favorable (HF) are patients up to 40 years of age presenting with stage I disease involving only one site of disease with a maximum tumor diameter (TD) of 5 cm and no adverse factors. In this group only mantle field irradiation is recommended if the disease is located in the neck or above, inverted-Y irradiation is recommended for distal subdiaphragmatic lesions, and subtotal nodal irradiation in all other cases. HF cases may also be treated like favorable cases with limited chemoradiation. Favorable (F) cases are patients in stage I with a TD greater than 5 cm and smaller than 10 cm or stage II, up to three sites of disease and negative prognostic factors for systemic disease. All other patients are included in the "not favorable" (NF) group at Ann Arbor stage I or II with any adverse prognostic factor. For the latter two groups, chemotherapy with the ABVD or Stanford V regimen precedes involved-field radiotherapy to sites with a TD of at least 5 cm. The total irradiation dose is determined by local disease extent and level of response to chemotherapy. Images on which the radiation fields are drawn serve as an important reference to improve the homogeneity of treatments. This protocol includes a list of adverse treatment effects (chemo- and/or radiotherapy) together with follow-up guidelines for the early detection of secondary cancers in previously irradiated patients.

Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in patients with cutaneous T-cell lymphoma.

PURPOSE: To evaluate the efficacy and side effects of psolaren with ultraviolet light A (PUVA) and interferon-alpha-2a (IFN-alpha-2a) in patients with mycosis fungoides (MF) and Sézary syndrome (SS). PATIENTS AND METHODS: From May 1993 to January 1999, 63 symptomatic patients with all stages of MF and SS were treated in a prospective Phase II trial with systemic escalating doses of IFN-alpha-2a combined with PUVA for 1 year, followed by indefinite PUVA maintenance in complete responding patients. RESULTS: Sixty-three patients were enrolled (Stage IA, n = 6; IB, n = 37; IIA, n = 3; IIB, n = 3; III, n = 12; IVA, n = 2). Ten patients had received previous therapy. The median follow-up duration for the entire cohort is 37 months. Of 63 patients, 51 achieved a complete response (CR; 74.6%) or partial response (PR; 6%) to therapy. The median response duration is 32 months. The 5-year overall survival rate is 91% and the 5-year disease-free survival rate is 75%. No life-threatening side effects were observed. Five patients stopped IFN-alpha-2a therapy due to toxicity. Eighty-four percent of the patients received more than 75% of the planned dose (12 million units three times a week). CONCLUSIONS: This combination of IFN-alpha-2a and phototherapy is an effective and safe therapy for patients with symptomatic MF.