[show abstract][hide abstract] ABSTRACT: The incidence of second non-breast primary cancer following adjuvant treatment was evaluated using data from patients enrolled from 1978 to 1999 in four International Breast Cancer Study Group (IBCSG) trials. The occurrence of these tumours as sites of the first failure was assessed separately for two treatment comparisons: toremifene versus tamoxifen for 5 years in 1035 patients in IBCSG Trials 12-93 and 14-93 with a median follow-up of 8 years and endocrine therapy (toremifene or tamoxifen) versus chemo-endocrine therapy (CMF or AC plus toremifene or tamoxifen) in 1731 patients from IBCSG Trials III, VII and 12-93, with a combined median follow-up of 14 years. No significant differences in second non-breast primary tumours were observed in either comparison. In particular, the incidences of second primary uterine tumours with toremifene and tamoxifen were similar and no significant increase of secondary leukaemias was observed with chemo-endocrine therapy compared with endocrine therapy.
European journal of cancer (Oxford, England: 1990) 01/2009; 45(4):561-71. · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lipoplatin is a liposome encapsulated form of cisplatin. Phase I studies on Lipoplatin showed an excellent toxicity profile
of the compound. Therefore we performed a phase II trial in heavily pre-treated patients with advanced non–small cell lung
This was an open label single-arm trial in patients with NSCLC with stage IV disease already pre-treated with first line chemotherapy.
63% of these patients were pre-treated with platinum containing regimens. Statistical analysis was performed with the SPSS
statistical program (version 11.0). Survival curves were estimated by the Kaplan Meyer method. We administered Lipoplatin
at the dose of 100 mg/m2 every 14 days as second line chemotherapy. The primary endpoint was the response rate. The secondary endpoints were safety,
time to progression and overall survival.
Nineteen patients with stage IV NSCLC, the median age being 64 were treated. Fifteen patients completed at least six cycles
and were evaluated for response and toxicity. Four patients completed one cycle of therapy and were evaluated only for toxicity.
We obtained one partial response (5.2%) and three stable diseases (15.9%). Median time to progression was 4 months and median
survival time was 7.2 months.
In this study lipoplatin as second line treatment showed a lower activity in comparison to other drugs, but the same overall
survival. New phase II studies with escalation of the dosage should be considered.
KeywordsLipoplatin–Non–small cell lung cancer–Phase II trial
[show abstract][hide abstract] ABSTRACT: GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy.
We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression.
Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar.
Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.
Supportive Care Cancer 02/2008; 16(1):67-74. · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials.
Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene.
Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty-five of 4948 (0.9%) patients had ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms.
Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints.
Cancer 03/2006; 106(3):505-13. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report three patients with advanced "hormone-resistant" prostate cancer, each of whom had rapid progression of the disease during treatment with megestrol acetate for cancer cachexia. All patients had been previously treated with total androgenic deprivation. With progression of the disease, megestrol acetate was given to palliate the cancer-related wasting syndrome. No other antineoplastic drugs were contemporaneously given, and no concomitant condition that could favor the progression of the disease was present. The worsening observed while receiving megestrol acetate, and the atypical withdrawal syndrome occurring after the treatment was stopped, seem to suggest a promoting role of megestrol acetate in advanced "hormone-resistant" prostate cancer. The risk of rapid disease progression overwhelming the anti-cachectic palliative effect should be kept in mind when progestins are administered as a palliative treatment of cancer cachexia in patients with advanced "hormone-resistant" prostate cancer.
Journal of Pain and Symptom Management 06/2003; 25(5):481-4. · 2.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer.
Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m(2) on the first day of each course and 5-FU and LV 350 mg/m(2) and 20 mg/m(2), respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses.
Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m(2). Reversible neurologic toxicity occurred in 44.4% of patients.
Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m(2) dosage offered improved dose-intensity compared with the initial dosage.
Journal of Clinical Oncology 06/2002; 20(10):2545-50. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Staging procedures used to detect metastatic breast cancer at the time of diagnosis are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS) and laboratory parameters (LP). These procedures are expensive and not all patients need them. We aimed to identify groups of patients with different risks for metastatic disease.
We reviewed data from 1,218 consecutive cases of breast cancer. Pathological and biological parameters and instrumental procedures performed at the time of diagnosis and during 6 months of follow-up were recorded. True positive and negative, false positive and negative cases were evaluated. All cases were grouped on the basis of tumour size, nodal involvement, biological characteristics, menopausal status and age.
We observed 46 (3.8%) true positive cases with metastatic disease at the time of diagnosis. Documentation relating to BS, CXR and LUS was available for 1,193, 1,206 and 1,206 patients, respectively, with 37 (3.1%), 8 (0.7%) and 10 (0.8%) true positive tests. Logistic regression analysis showed significant odds ratio estimates for pT status and nodal status, thus highlighting the role of these morphological data. These findings suggest that breast cancer patients can be divided into two subgroups: first group pT1-3N0-1. with < or = 3 involved nodes, and second group pT1-3N1 with > or = 4 involved nodes, pT4 and pN2 (metastases detection rate 1.46 and 10.68%, respectively). In the former group the appropriate procedures of staging would only be laboratory parameters, whereas in the latter group BS, CXR, LUS, LP and tumour markers CEA and CA 15.3 would.be necessary.
The standard staging procedures to detect metastatic disease at breast cancer diagnosis require modification. On the basis of the literature data and our findings, the full staging procedure is appropriate in the second group of patients.
Breast Cancer Research and Treatment 04/2002; 72(1):53-60. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: A registry-based cohort study of male patients with bladder cancer was conducted to determine the relative risk of second primary cancer of the prostate and kidney, the uni-/multivariate differences in relative risk according to patient characteristics, the cumulative risk by duration of the follow-up, and the prevalence:incidence ratio of prostate and kidney cancer cases detected in the first 6 months after the diagnosis of bladder cancer.
The complete case records of all male patients (n = 2025) diagnosed with bladder cancer between 1986 and 2002 were extracted from the database of the Romagna Cancer Registry: 1539 patients were eligible for analysis of the incidence of following prostate and kidney cancers, of the relative risk and the standardized incidence ratio specific for the time interval of follow-up.
A total of 108 prostate cancer cases and 23 kidney cancer cases were observed during the follow-up. The relative risk of second primary cancer of the prostate and kidney was respectively 3.52 (95% CI, 2.89-4.25) and 3.90 (95% CI, 2.47-5.85). The absolute excess risk was 11.8 x 1000 for prostate cancer and 2.5 x 1000 for kidney cancer. The number of prevalent cases of prostate and kidney cancer detected was approximately 10 times greater than the expected number based on incidence rates from the general population. During the follow-up, incidence of prostate cancer stabilized at a level that was 3- to 4-fold greater than that expected. Despite fluctuations, a decrease was also observed for incidence of kidney cancer.
In summary, our study showed the relatively constant high incidence of prostate and kidney cancers in bladder cancer patients over time. The possibility of subsequent cancer implies that an appropriate long surveillance is required. The pertinence depends on the duration of the follow-up as well as the degree of surveillance.
[show abstract][hide abstract] ABSTRACT: According to the USA Food and Drug Administration, quality of life (QOL) and/or survival are a priority for new anticancer drug approval. This study was performed to review approaches to QOL in randomized controlled clinical trials (RCCTs) and to survey the use of such measures in trials.
A literature survey was carried out using the Medline/Medscape, Embase, Cochrane Library, and Ovid databases. Included in the survey were all publications in the set period (from 1966 to June 2005) with "quality of life" in the title or in the abstract in the field of "randomized, controlled clinical trials". Each trial was evaluated according to the level of importance of QOL as a measure of outcome (primary, important and secondary) and was analyzed using the quality scoring system reported by Nicolucci et al. with some items regarding QOL.
Four hundred and five RCCT articles in the oncology setting were found. Fifty-six of the 405 (13.8%) publications had QOL as primary end point. The overall quality score of these trials ranged from 40% to 100%, with a median overall score of 80%. The overall score was correlated with the year of publication (P = 0.007), the type of journal (P = 0.05), the presence of a biostatistician among the authors (P = 0.001), and the number of participating institutions (P = 0.009).
More attention to QOL in all components of RCCTs (design, choice of instruments, data management and processing) is required from both clinicians and statisticians.
[show abstract][hide abstract] ABSTRACT: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC.
Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method.
After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84).
Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.
[show abstract][hide abstract] ABSTRACT: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial.
Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response.
After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003).
Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.