Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer)

Background: First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. Patients and methods: Women with stage III or IV breast cancer aged >_70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m2 was administered weekly for 3 weeks every 28 days. Results: Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5\u201318.7) and median survival was 35.8 months (95% CI 19\u2013not defined). Conclusions: Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherap

Carboplatin plus paclitaxel in extensive small cell lung cancer: a multicentre phase 2 study

A multicentre phase 2 trial (single-stage design) was undertaken to test the efficacy and toxicity of carboplatin (AUC 6 according to Calvert) plus paclitaxel (175 mg/m23-h infusion) every 4 weeks in the first line treatment of patients affected by extensive small cell lung cancer. The primary end-point of the trial was the objective response rate. 31 objective responses among 50 patients were considered necessary to proceed to a phase 3 trial. 48 patients were enrolled (median age 59 years). Treatment was very well tolerated. 3 patients (6.2%) had a complete response and 23 (47.9%) a partial response, for an overall response rate of 54.2% (95% CI: 39.2–68.6) Median time to progression was 5.7 months (95% CI: 5.2–6.2). Median survival was 9.6 months (95% CI: 7.2–14.6), with a median follow-up time of alive patients of 12 months. At 1 year, the probability of being progression-free or alive was 0.16 and 0.43, respectively. In conclusion, carboplatin plus paclitaxel as given in the present study is very well tolerated but not sufficiently active to warrant phase 3 comparison with standard chemotherapy regimens. © 2001 Cancer Research Campaign http://www.bjcancer.co

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment

\u201cA randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer\u201d

The sequential doxorubicin \u2192 CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF 7 6 cycles (CMF); (b) doxorubicin 7 4 cycles followed by CMF 7 6 cycles (A \u2192 CMF); (c) CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (CMF \u2192 GT); and (d) doxorubicin 7 4 cycles followed by CMF 7 6 cycles followed by goserelin plus tamoxifen 7 2 years (A \u2192 CMF \u2192 GT). The study used a 2 7 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A 7 CMF or arms a + c vs b + d) and (2) the effect of adding GT after chemotherapy (arms a + b vs c + d). At a median follow-up of 72 months, A \u2192 CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR) = 0.740 (95% confidence interval (CI): 0.556-0.986; P = 0.040) and produced a nonsignificant improvement of overall survival (OS) (HR = 0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR = 0.74; 95% CI: 0.555-0.987; P = 0.040), with a nonsignificant improvement of OS (HR = 0.84; 95% CI: 0.54-1.32). A \u2192 CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients. \ua9 2005 Cancer Research UK

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study

The aims of this multicentre, randomised phase III trial were to evaluate: ( 1) the role of levamisol (LEV); and ( 2) the role of folinic acid ( FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2 x 2 factorial design with four treatment arms: ( a) 5FU alone, (b) 5FU+LEV, ( c) 5FU+FA, ( d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73 - 1.09) for patients receiving FA and 0.99 ( 95% CI 0.80 - 1.21) for those receiving LEV; corresponding HRs of death were 1.02 ( 95% CI: 0.80 - 1.30) and 0.94 ( 95% CI 0.73 - 1.20). Nonhaematological toxicity ( all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients

Phase II study of sequential hormonal therapy with anastrozole/exemestane in advanced and metastatic breast cancer

Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted ≥ 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy. © 2005 Cancer Research UK

Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection

Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens