Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients.

AIM: This observational study investigates the use of adjuvant trastuzumab (AT) in HER2-positive breast cancer patients in a real-life setting, focusing on relapse and discontinuation rates. PATIENTS & METHODS: Data on a group of HER2-positive patients collected from 13 oncology centers of northeast Italy were analyzed. RESULTS: In total, 1245 patients were analyzed. 13.1% of patients were excluded from AT because of comorbidities, age, tumor stage, refusal or other reasons; 8.2% of patients who received AT interrupted the therapy, mainly for toxicity. Overall the relapse rate was 10.9% in the AT-treated population versus 22.6% in nontreated patients (follow-up: 37.4 and 62.1 months, respectively). Disease-free survival (DFS) was lower in AT-relapsed patients than in not-relapsed. Statistical analysis showed a correlation between DFS and estrogen receptor status in AT-treated patients. CONCLUSION: Relapse rates are lower in clinical setting compared to clinical trials. Overall, AT is effective in HER2-positive early-stage breast cancer patients.

Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study.

This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m(-2) day days 1-14, LV 90 mg day days 1-14, irinotecan 240 mg m(-2) day 1; q21) or TEGAFOX (UFT 250 mg m(-2) day days 1-14, LV 90 mg day days 1-14, oxaliplatin 120 mg m(-2) day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3-4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1-55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6-51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12-23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies.

Simplified gemcitabine and platin regimen in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to be proposed as neoadjuvant therapy.

BACKGROUND: Chemotherapy of non-small-cell lung cancer (NSCLC) has been improved by the use of cis-platin (P) and the pyrimidine antimetabolite gemcitabine (G) (2',2'-difluorodeoxycytidine). GP regimens currently used in Italy for NSCLC were and are mainly based on G day 1, 8 and 15; P on day 2, every 28 days (4 Day-Hospital admissions per cycle). However, the third G dose is frequently omitted because of myelo-toxicity, with a consistent dose decrease of both G and P in comparison with the intended dose. The 24-h lag time from 1(st) G and P has not reasonable clinical pharmacology base. AIM OF THE STUDY: To have a simplified GP regimen based on two Day-Hospital admissions per cycle, with G on day 1 and 8, P after G on day 8; every 21 days, with the goal to use it in the neoadjuvant setting. MATERIAL AND METHODS: The study was designed as a controlled, prospective, multicentre investigation, based on G (1500 mg/m(2)) on day 1 and 8, and P (100 mg/m(2)) on day 8 immediately following G, administered on a 3-week cycle. Quality of life (EORTC) was valuated in 46 patients out of 95 valuable patients. Restaging procedures were repeated after the 3rd and the 6th cycle. RESULTS: Enrolled patients were 105 (stage IV: 63: IIIB: 29; IIIA: 13). GP cycles were 488 (1 to 6 per patient) 95 patients had at least 3 cycles and 59 of them had further 3 cycles. Myelotoxicity >or= g3 was mainly neutropenia, easily amenable with symptomatic and GCSF therapies (12.6% neutropenic fever); PNS toxicity occurred in 17.9% of patients. QoL was ameliorated (P < 0.05). Therapy was tolerable and gave a Response Rate (RR) of 52.3% after 3 cycles (Intention-to-treat analysis) and of 57.9% in 95 valuable patients who received at least 3 therapy cycles. CONCLUSION: Present results confirm a good efficacy and/or synergism of G to P, with G on day 1 and 8 and P on day 8. This two day-hospital admissions regimen is at least as good as more complex GP regimens, and may be proposed in the neoadjuvant setting.

Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC).

This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m(-2) per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m(-2) day(-1) for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5-16% and 2-22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25-101 weeks) for GEM and 26 weeks (range 16-46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2-65 weeks) and 18 weeks (range 4-51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1-101 weeks) and 30 weeks (1-101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.

Fatigue in cancer patients receiving chemotherapy: an analysis of published studies.

Fatigue is a subjective experience that affects everybody. In healthy individuals, it can be considered a physiological response to physical or psychological stress. In people with specific diseases, however, fatigue often represents one of the most significant problems. Fatigue can be caused by many factors, both intrinsic to the patient and extrinsic, such as therapeutic interventions. This review, based on published studies, has been conducted with the aim of presenting a critical discussion of the available information on the characteristics, causes and potential treatments of fatigue in cancer patients receiving chemotherapy. The incidence of fatigue in these patients, the methods for measuring and evaluating fatigue, and possible therapeutic options are discussed. An appraisal of the toxicity of various chemotherapeutic agents is also presented. Although fatigue is now an ever more considered aspect of the toxicity of chemotherapy, it remains difficult to establish what standard should be used to make a quali-quantitative evaluation of this symptom. Furthermore, in the absence of a clear demonstration of the efficacy of some therapies, the management of cancer-related fatigue remains poorly defined (except for the treatment of anemia-related fatigue). New randomized clinical trials are necessary to indicate the best strategies for tackling this important problem.

Preoperative chemoradiotherapy in cancer of the thoracic esophagus.

Surgery with or without adjuvant radiotherapy (RT) is the standard treatment of esophageal cancer. Preoperative radio- and chemotherapy (CT) have been introduced to improve prognosis. We report a phase II prospective non-randomized trial of preoperative RT (42 Gy/25) plus CT (cisplatin 20 mg/mq/day plus 5-fluorouracil 600 mg/mq/day, 1-5 weeks) for the treatment of thoracic esophageal cancer. From 1993, 50 patients were enrolled (40 men and 10 women, mean age 57 years, range 30-75 years). Squamous cell carcinoma accounted for 90% of cases; 10% were adenocarcinoma. Downstaging of the disease was obtained in 77.3% of cases; there were 13 (29.5%) complete responses (CR) and 21 (47.7%) partial responses (PR). Median survival was 28 and 25 months, respectively, for CR and partial response (PR) plus stable disease (SD) and progressive disease (PD) (P = 0.05). Progressive-free median survival was 22 and 17 months, respectively, for CR and PR + SD + PD (P = 0.08). Multimodal treatment of esophageal cancer showed promising results, although not significant, in terms of survival and disease progression for patients achieving a complete pathologic response.

Cisplatin and gemcitabine in non-small-cell lung cancer.

The nucleoside analogue, gemcitabine, has shown activity as a single agent in the treatment of metastatic non-small-cell lung cancer (NSCLC), producing consistent response rates of 20% and above. Because of its unique mechanism of action and its non-overlapping toxicity with other active agents, gemcitabine is an attractive candidate for trials in combination with other cytotoxic agents. In preclinical models, the cisplatin-gemcitabine combination suggested synergy between the two drugs. In phase I-II studies, response rates are as high as 54% when gemcitabine is combined with cisplatin, both in stage III and IV NSCLC. The gemcitabine-containing regimens showed a favourable safety-efficacy profile and compared well with standard regimens used in NSCLC. These preliminary results must be validated by large randomised trials comparing gemcitabine-containing regimens with NSCLC reference chemotherapy regimens.

Vinorelbine, bleomycin and methotrexate as a salvage therapy for patients with head and neck squamous carcinoma in relapse after cisplatin/fluorouracil.

BACKGROUND: Cisplatin (CDDP) and 5-fluorouracil (5-FU) represent the standard chemotherapy for advanced/recurrent head and neck squamous carcinoma (HNSC); however, the duration of response is often short, with a median survival of only five to six months. PATIENTS AND METHODS: Patients with HNSC were treated with vinorelbine 20 mg/m2 and methotrexate 50 mg/m2 every week and bleomycin 15 mg/m2 every two weeks. All patients were previously treated with a CDDP/5-FU regimen. RESULTS: Forty-eight patients were evaluable for response and toxicity. After a median follow-up of 15 months, 16 patients are still alive and 32 have died. We had one complete response (2%), 12 partial responses (25%) (overall response rate 27%; 95% CI: 14%-39%), 11 stabilizations (23%) and 24 progressions (50%) of disease. Neutropenia grade 3-4 was seen in 12 patients; peripheral neurotoxicity in two patients. There were no toxic deaths. CONCLUSIONS: This regimen, administered in an outpatient setting, revealed some activity as a second-line treatment in patients with HNSC, with acceptable toxicity.

Mitomycin C, cisplatin, and 5-fluorouracil for advanced and/or recurrent head and neck squamous cell carcinomas.

The combination of cisplatin (CDDP 100 mg/m2 on day 1) and 5-fluorouracil (5-FU 1,000 mg/m2 continuous intravenous (i.v.) infusion days 1-5) is the most widely used chemotherapy regimen for the treatment of advanced head and neck carcinomas, with a response rate of 70-90% but with a survival and a duration of response which are not impressive. Most patients relapse in < or = 2 years and die of cancer. We evaluated the activity of a CDDP (90 mg/m2 on day 1), 5-FU (900 mg/m2/120 h continuous i.v. infusion from day 1), and mitomycin C (MMC 6 mg/m2 on day 1) regimen in advanced or recurrent head and neck squamous cell carcinoma (HNSCC). Fifty-six patients were treated and evaluated for response and toxicity: 5 (9%) complete responses (CR) and 36 (64%) partial responses, (PR) were observed (response rate 73%). The median duration of response was 12 months, and median survival was 15 months. At a median follow-up of 14 months, the estimated overall survival at 1 year was 65%; at 2 years, it was 35%. Grade 3-4 toxicity was noted in 14 patients, mostly hematologic; overall toxicity required a dose-intensity decrease in 20.2% of all cycles. No treatment-related deaths occurred. The regimen showed a good response rate and an encouraging median duration of response with a good tolerability profile.