Breast cancer patients enrolled in the Swiss mammography screening program "donna" demonstrate prolonged survival.

STUDY GOAL: We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) "donna". METHODS: We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. RESULTS: We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p < 0.01), a smaller (mean) tumor size (19.1 mm vs. 24.9 mm, p < 0.01), and fewer recurrences and metastases in the follow-up period (6.7% vs. 15.6%, p < 0.01). The 10-year survival rates were 91.4% for women within and 72.1% for women outside the MSP (p < 0.05). Survival difference persisted but decreased when women within the same tumor stage were compared. Lead-time corrected hazard ratios for the MSP accounted for age, tumor size and Ki-67 proliferation index were 0.550 (95% CI 0.389, 0.778; p < 0.01) for overall survival and 0.469 (95% CI 0.294, 0.749; p < 0.01) for BC related survival. CONCLUSION: Women participating in the "donna" MSP had a significantly higher overall and BC related survival rate than women outside the program. Detection of BC at an earlier tumor stage only partially explains the observed differences.

Critical Evaluation of Transcripts and Long Noncoding RNA Expression Levels in Prostate Cancer Following Radical Prostatectomy.

INTRODUCTION: The clinical course of prostate cancer (PCa) is highly variable, ranging from indolent behavior to rapid metastatic progression. The Gleason score is widely accepted as the primary histologic assessment tool with significant prognostic value. However, additional biomarkers are required to better stratify patients, particularly those at intermediate risk. METHODS: In this study, we analyzed the expression of 86 cancer hallmark genes in 171 patients with PCa who underwent radical prostatectomy and focused on the outcome of the 137 patients with postoperative R0-PSA0 status. RESULTS: Low expression of the IGF1 and SRD52A, and high expression of TIMP2, PLAUR, S100A2, and CANX genes were associated with biochemical recurrence (BR), defined as an increase of prostate-specific antigen above 0.2 ng/mL. Furthermore, the analysis of the expression of 462 noncoding RNAs (ncRNA) in a sub-cohort of 39 patients with Gleason score 7 tumors revealed that high levels of expression of the ncRNAs LINC00624, LINC00593, LINC00482, and cd27-AS1 were significantly associated with BR. Our findings provide further evidence for tumor-promoting roles of ncRNAs in PCa patients at intermediate risk. The strong correlation between expression of LINC00624 and KRT8 gene, encoding a well-known cell surface protein present in PCa, further supports a potential contribution of this ncRNA to PCa progression. CONCLUSION: While larger and further studies are needed to define the role of these genes/ncRNA in PCa, our findings pave the way toward the identification of a subgroup of patients at intermediate risk who may benefit from adjuvant treatments and new therapeutic agents.

Screening is associated with lower mastectomy rates in eastern Switzerland beyond stage effects.

BACKGROUND: A recent study found an influence of organized mammography screening programmes (MSPs) on geographical and temporal variation of mastectomy rates. We aimed to quantify the effect on the example of one of the cantonal programmes in Switzerland. METHODS: We used incidence data for the years 2010-2017 from the cancer registry of Eastern Switzerland. We included women with invasive-non-metastatic breast cancer (BC) in the screening age group 50-69-year-olds in the canton of St.Gallen. We compared mastectomy rates among cancer patients detected through the organised screening programme (MSP) vs. otherwise detected by stage. RESULTS: MSP-detected patients in St.Gallen presented with lower stages. 95% of MSP-detected had stages I-II vs 76% of Non-MSP-detected. Within all non-metastatic stage, tumour size and nodal status groups, MSP-detected patients had lower mastectomy rates, overall 10% vs 24% in 50-69-year-old non-participants. Their odds of receiving a mastectomy are about half of the Non-MSP-detected (OR = 0.48, p = 0.002). CONCLUSIONS: Our study showed that MSPs have a positive effect on lowering mastectomy rates. Screening participants are significantly less likely to receive a mastectomy compared to non-participants, which must be attributed to additional factors than just lower stages. Lower mastectomy rates lead to a higher quality of life for many patients.

A Phase II Study of the Central European Society of Anticancer-Drug Research (CESAR) Group: Results of an Open-Label Study of Gemcitabine plus Cisplatin with or without Concomitant or Sequential Gefitinib in Patients with Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium.

INTRODUCTION: This phase II trial evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, in combination with first-line chemotherapy in advanced urothelial cancer. METHODS: Chemotherapy-naïve patients with advanced or metastatic urothelial carcinoma were randomized 1:1:1 to receive six cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8, and cisplatin 70 mg/m2 on day 1 of every cycle) concomitantly with gefitinib 250 mg/day (arm A); or with sequential gefitinib (arm B); or alone (arm C). The primary endpoint was the time to progression (TTP). RESULTS: A total of 105 patients received study treatment. Median TTP for arms A, B, and C were 6.1, 6.3, and 7.8 months, respectively. There were no significant differences between treatment arms for any outcomes measured. The most common adverse events were nausea and vomiting. CONCLUSION: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.

Multidisciplinary care in patients with prostate cancer: room for improvement.

PURPOSE: New multimodality treatment approaches for prostate cancer require multidisciplinary management of patients. We aimed to assess the current practices of multidisciplinarity and their possible implications in treatment management in Switzerland. METHODS: In a survey, urologists and medical oncologists in Switzerland were asked to include at least 25 or 15 consecutive patients with the diagnosis of prostate cancer, respectively. Information about treatment patterns and multidisciplinary parameters of these patients was collected retrospectively. RESULTS: Thirty-seven urologists and 20 oncologists from the French- and German-speaking parts of Switzerland representing 7 out of 11 non-university tertiary centres and 20/10 % of all office-based urologists/oncologists in Switzerland collected data on 1,184 patients. Sixty-five percent of the office-based (16/24 urologists; 6/10 oncologists) and 95 % of the hospital-based (10/11 urologists; 8/8 oncologists) physicians participate in multidisciplinary tumour boards (MTBs). However, only 1.5 % of patients with a new diagnosis of prostate cancer (13 of 883) are discussed at a MTB. Overall, second opinions at diagnosis are requested in 23 % of patients, mainly from radiation oncologists (8.4 %) or fellow urologists (7.4 %). Second opinions are more often requested by urologists who participate at MTBs and in case of advanced stage. CONCLUSIONS: Participation at MTBs is high among Swiss urologists and oncologists in private practice and at non-university tertiary centers. In spite of that only a small minority of patietns with prostate cancer are presented at MTBs.

[Principle and practice of clinical phase III studies]. / Planung und Durchführung klinischer Phase-III-Studien.

Randomized phase III studies compare new treatments with standard therapy according to defined guidelines and legal rules. Large international randomized phase III studies are some of the most complex and expensive medical experiments. The results of such trials will decide about the future of new drugs and are the basis of evidence-based medicine and the development of clinical guidelines. This contribution discusses randomization, endpoints, inclusion and exclusion criteria of phase III trials as well as further challenges when developing and conducting phase III studies in oncology.

Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

BACKGROUND: The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. PATIENTS AND METHODS: Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. RESULTS: One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. CONCLUSION: Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found.

A phase II, open-label study of gefitinib (IRESSA) in patients with locally advanced, metastatic, or relapsed renal-cell carcinoma.

Epidermal growth factor receptor (EGFR) expression has been associated with clinical outcome in some studies of renal-cell carcinoma (RCC). We investigated the efficacy and safety of gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, in RCC patients. This phase II trial recruited 28 patients with advanced, metastatic, or relapsed RCC. Patients received oral gefitinib 500 mg/day. Objective responses (ORs) were assessed every 2 months according to RECIST. Baseline tumor biopsies were analyzed immunohistochemically for EGFR expression. At trial closure (March 2003), no ORs were seen but 14 patients (53.8%) had stable disease. At extended analysis (August 2004), median time to progression was 110 days (95% confidence interval [CI]: 55, 117); median overall survival was 303 days (95% CI 180, 444). Gefitinib was generally well tolerated. Skin rash and diarrhea were the most common drug-related adverse events (AEs) [54 and 39% of patients, respectively] and the most common drug-related grade 3/4 AEs (both 11%). The majority of tumor biopsies (91%) had > or =70% of tumor cells expressing membrane EGFR. Despite the lack of ORs in this study, disease control was observed in 53.8% of patients. Gefitinib was generally well tolerated and no unexpected drug-related AEs were observed.

Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast cancer.

High serum concentrations of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of breast, prostate, colorectal, and lung cancer whereas IGF binding protein-3 (IGFBP-3) seems to exert a protective effect. Therefore, patients may benefit from low IGF-1 levels and high IGFBP-3 levels. This study evaluated whether adjuvant anthracycline-containing chemotherapy modulates IGF-1 and/or IGFBP-3 serum levels in breast cancer patients. In 18 patients undergoing adjuvant treatment for primary breast cancer, IGF-1 and IGFBP-3 serum levels were measured with immunoassays during chemotherapy regimens of either 5-fluorouracil, epirubicin and cyclophosphamide (FEC) or epirubicin and cyclophosphamide (EC). Mean pre-treatment values of IGF-1 and IGFBP-3 were 124+/-13 and 3698+/-186 ng/ml, respectively. No significant changes in IGF-1 and IGFBP-3 serum concentrations were observed during adjuvant anthracycline-containing chemotherapy. IGF-1 levels significantly correlated with IGFBP-3 levels before and during chemotherapy. In conclusion, these chemotherapy regimens do not seem to modulate IGF-1 or IGFBP-3 levels in a favourable or unfavourable way.

Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression.

Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered "housekeeping" genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa. We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient-derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing. Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non-metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse-free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro-inflammatory cytokine expression in PCa. Our results demonstrate that SNORA55 up-regulation predicts PCa progression and that silencing this non-coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target.

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients naïve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.

Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer.

PURPOSE: To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer. PATIENTS AND METHODS: Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study. RESULTS: The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively. CONCLUSION: Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.

Focus on cancer prevention.

Tumor Prevention and Genetics 2002, the 2nd International Conference and 7th Annual Meeting of The International Society of Cancer Chemoprevention (ISCaC) was held in St. Gallen, Switzerland, 14-16 February 2002.

Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned. PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR. RESULTS: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC. CONCLUSION: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.

Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: phase II randomized study comparing two dose levels.

BACKGROUND: Systemic IL-2 has shown some activity in metastatic melanoma, but its use is severely limited by toxicity. TG2001 is a product in which the human IL-2 cDNA was incorporated into the genome of Vero cells, a monkey fibroblast cell line. The goal of this intratumorally applied therapy was to create an antitumor immune response stimulated by xeno-antigens and local production of IL-2 in the close vicinity of tumor-specific antigens. TG2001 was reported to have a good safety profile in two previous dose-escalating phase I studies performed in 18 patients with various solid tumors, with encouraging clinical responses in three patients. The objectives of this study were to evaluate the tolerance and incidence of tumor regression in patients with metastatic melanoma, following repeated administration of Vero-IL-2 cells. PATIENTS AND METHODS: This was on open-label, randomized phase II study comparing two doses of Vero-IL-2, 5x10(5) and 5x10(6) cells. Twenty-eight patients with metastatic melanoma were enrolled in the study, 14 in each treatment group. Patients received TG2001 by intratumoral injection on days 1, 3, and 5 every 4 weeks for four cycles, and every 8 weeks thereafter, until evidence of progressive disease (PD). Criteria for patient selection included histologically proven metastatic melanoma, with one tumor accessible for product administration, and at least another tumor site for response assessment. Evaluation included tumor measurements, humoral and T cell-mediated local and systemic immune response, humoral response to Vero cells, adverse events and standard laboratory parameters. RESULTS: None of the patients achieved a confirmed objective response. Stable disease (SD) was seen in six (43%) and eight patients (57%) at the 5x10(5) and the 5x10(6) dose level, respectively. Two patients, one in each group, died during the study (i.e., within 1 month after the last injection) due to PD. Three patients exhibited antibody responses to Vero cells. T-cell immunity, serum cytokine levels and cytokine mRNA expression in tumor biopsies did not show meaningful alterations after therapy, except for a trend toward an increase in intratumoral TH2 cytokine (IL-4 and/or IL-10) levels. The study drug was well tolerated at both dose levels and side effects mainly consisted of injection site pain and erythema, and pyrexia. CONCLUSION: The intratumoral administration of TG2001 was generally well tolerated in patients with metastatic melanoma, and transient disease stabilization was observed in 50% of patients.

Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer.

Metastatic prostate cancer (PCa) is still an incurable disease. Long non-coding RNAs (lncRNAs) may be an overlooked source of cancer biomarkers and therapeutic targets. We therefore performed RNA sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The most highly up-regulated transcript was LOC728606, a lncRNA now designated PCAT18. PCAT18 is specifically expressed in the prostate compared to 11 other normal tissues (p<0.05) and up-regulated in PCa compared to 15 other neoplasms (p<0.001). Cancer-specific up-regulation of PCAT18 was confirmed on an independent dataset of PCa and benign prostatic hyperplasia samples (p<0.001). PCAT18 was detectable in plasma samples and increased incrementally from healthy individuals to those with localized and metastatic PCa (p<0.01). We identified a PCAT18-associated expression signature (PES), which is highly PCa-specific and activated in metastatic vs. primary PCa samples (p<1E-4, odds ratio>2). The PES was significantly associated with androgen receptor (AR) signalling. Accordingly, AR activation dramatically up-regulated PCAT18 expression in vitro and in vivo. PCAT18 silencing significantly (p<0.001) inhibited PCa cell proliferation and triggered caspase 3/7 activation, with no effect on non-neoplastic cells. PCAT18 silencing also inhibited PCa cell migration (p<0.01) and invasion (p<0.01). These results position PCAT18 as a potential therapeutic target and biomarker for metastatic PCa.

The antihormonal preventive therapy of breast cancer and prostate cancer.

With the continuing increase of median life expectancy of important segments of the world's population, cancer incidence, as well as cancer related morbidity and mortality, are constantly increasing, especially for developing countries and for breast and prostate cancer, the predominant gender-associated cancer types. In addition to continuing, with more and more expensive efforts to develop new and more effective cancer treatments, it is health-politically and medico-professionally important to realise that only successful approaches to primary cancer prevention of major and frequent cancer types will be able to change this socially and economically unfavourably outlook. It is therefore encouraging to see that primary (or pharmacologic, interventional) cancer prevention programs have been successfully developed over the past decade for individuals at elevated risk for breast and prostate cancer on the basis of several scientifically well-conducted, prospective chemoprevention trials, mainly with synthetic anti-hormones (anti-estrogens and anti-androgens) in the USA, in Europe and Australia. This paper summarises the presently published results and design of several completed and some currently running primary cancer prevention trials in breast cancer and prostate cancer, and also points to the important obstacles for their conduct and translation into general practice in the broader populations at risk outside of clinical prevention research.

An open-label, noncomparative phase II trial to evaluate the efficacy and safety of docetaxel in combination with gefitinib in patients with hormone-refractory metastatic prostate cancer.

BACKGROUND: Prostate cancer is the most common type of cancer in men, however, therapeutic options are limited. 50-90% of hormone-refractory prostate cancer cells show an overexpression of epidermal growth factor receptor (EGFR), which may contribute to uncontrolled proliferation and resistance to chemotherapy. In vitro, gefitinib, an orally administered tyrosine kinase inhibitor, has shown a significant increase in antitumor activity when combined with chemotherapy. PATIENTS AND METHODS: In this phase II study, the safety and efficacy of gefitinib in combination with docetaxel, a chemotherapeutic agent commonly used for prostate cancer, was investigated in patients with hormone-refractory prostate cancer (HRPC). 37 patients with HRPC were treated continuously with gefitinib 250 mg once daily and docetaxel 35 mg/m2 i.v. for up to 6 cycles. PSA response, defined as a =50% decrease in serum PSA compared with trial entry, was the primary efficacy parameter. PSA levels were measured at prescribed intervals. RESULTS: The response rate and duration of response were consistent with those seen with docetaxel monotherapy. The combination of docetaxel and gefitinib was reasonably well tolerated in this study. CONCLUSION: Future studies should investigate whether patients with specific tumor characteristics, e.g. EGFR protein overexpression, respond better to gefitinib than patients without, leading to a more customized therapy option.

Continuous prednisolone versus conventional prednisolone with VMCP-interferon-alpha2b as first-line chemotherapy in elderly patients with multiple myeloma.

We report on a randomised trial that aimed to compare the efficacy of continued daily prednisolone treatment during the entire induction phase, with prednisolone given for 2 weeks of each cycle in combination with VMCP (vincristine, melphalan, cyclophosphamide, prednisolone)-interferon-alpha 2b (IFN-alpha 2b) treatment in 299 previously untreated elderly patients (median age: 67 years) with multiple myeloma. After completion of induction treatment patients were randomised to IFN-alpha 2b with or without prednisolone, thrice weekly. Response rate was 62% in the continuous and 60% in the control arm (intent to treat analysis, P=0.81). Progression-free survival [median: 20 months vs. 19 months; hazard ratio (HR): 0.99, 95% confidence interval (CI): 0.74-1.33, P=0.97] and overall survival (median: 34 months vs. 37 months; HR: 1.16, 95% CI: 0.85-1.59, P=0.35) were similar in both groups. Reduced performance status (Eastern Cooperative Oncology Group, grades 2-4) was the predominant risk factor for poor survival followed by age >65 years, high beta2-microglobulin, and impaired renal function. There was more grades 3-4 dyspnoea and cardiac impairment and grades 1-2 hyperglycaemia, but less nausea, emesis and anaemia in patients on continuous prednisolone therapy. In conclusion, continuing prednisolone treatment during the entire duration of the induction phase with VMCP-IFN-alpha 2b did not improve outcome.