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Biomedical subjects

Peter Schmid

Publications and source records attributed to Peter Schmid.

At least 19 recordsLinked to original sources
PubMed2026

Pembrolizumab plus chemotherapy followed by pembrolizumab in participants in Asia with early triple-negative breast cancer: An updated subgroup analysis of the KEYNOTE-522 randomized clinical trial.

BACKGROUND: In KEYNOTE-522 (NCT03036488), addition of perioperative pembrolizumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR), event-free survival (EFS), and overall survival (OS) in early-stage triple-negative breast cancer (TNBC). pCR and EFS results in participants enrolled in Asia were consistent with those in the overall population. We report OS, updated EFS, and safety outcomes in participants enrolled in Asia. METHODS: Participants with newly diagnosed, high-risk, early-stage TNBC (T1c [N1‒N2] or T2‒T4 [N0‒N2] per AJCC 7th edition) were randomized 2:1 to 8 cycles of neoadjuvant pembrolizumab 200 mg Q3W or placebo plus chemotherapy. After definitive surgery, participants received adjuvant pembrolizumab 200 mg Q3W or placebo for ≤9 cycles. Primary endpoints were pCR (ypT0/Tis ypN0) and EFS. OS was a secondary endpoint. RESULTS: Of 1174 randomized participants, 216 were enrolled in Asia. At data cutoff (March 22, 2024), EFS events occurred in 18/136 participants (13.2%) in the pembrolizumab + chemotherapy group versus 22/80 (27.5%) in the placebo + chemotherapy group (HR, 0.43 [95% CI, 0.23‒0.81]); 60-month EFS rates (95% CIs) were 87.4% (80.6%‒92.0%) and 72.1% (60.7%‒80.6%), respectively. In the respective groups, 12/136 (8.8%) and 16/80 participants (20.0%) died (HR, 0.41 [95% CI, 0.19‒0.86]); 60-month OS rates (95% CIs) were 91.9% (85.8%‒95.4%) and 81.1% (70.5%‒88.1%). Treatment-related AEs led to treatment discontinuation in 19/136 participants (14.0%) with pembrolizumab + chemotherapy and 7/79 (8.9%) with placebo + chemotherapy. CONCLUSIONS: OS and updated EFS outcomes in KEYNOTE-522 participants enrolled in Asia were consistent with those in the overall population and support use of perioperative pembrolizumab + neoadjuvant chemotherapy as a standard-of-care treatment in this setting.

Adjuvant↗
PubMed2007

Persistent organic pollutants, brominated flame retardants and synthetic musks in fish from remote alpine lakes in Switzerland.

Remote alpine lakes do not receive any direct aquatic inputs from anthropogenic activities. Therefore, these ecosystems may receive persistent organic compounds (POPs) by direct atmospheric deposition, only. Consequently, fish dwelling in these ecosystems represent an excellent indicator for the long-term atmospheric input of bioaccumulating and persistent contaminants. In the present study, fish from seven remote alpine lakes, located between 2062 and 2637 m above sea level in south eastern Switzerland (Grisons), were investigated. Lipid-based fish tissue concentrations of pesticides including dichlorodiphenyltrichloroethane (DDT) and its transformation products (2,4'-DDT, 4,4'-DDT, 2,4'-dichlorodiphenyldichloroethane (DDD), 4,4'-DDD, 2,4'-dichlorodiphenyldichloroethene (DDE), 4,4'-DDE), as well as dieldrin, heptachlor exo-epoxide (HPEX), hexachlorobenzene (HCB), hexachlorocyclohexanes (HCH), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F), and polybrominated diphenyl ethers (PBDE) were measured. In addition, seven synthetic musk compounds (Crysolide (ADBI), Phantolide (AHMI), Fixolide (AHTN), Traseolide (ATII), Galaxolide (HHCB), musk ketone (MK), and musk xylene (MX)) were determined. Concentrations of PCB, PCDD/F, and PBDE were in the same range as in fish from the major lakes situated in the Swiss plateau, indicating mainly atmospheric input of these persistent compounds. In contrast, concentrations of synthetic musks which are used as fragrances in laundry detergents and cosmetic products were distinctly lower than concentrations in fish from Swiss plateau lakes which receive inputs from waste water treatment plants.

Animals↗
PubMed2007

The historical record of PCB and PCDD/F deposition at Greifensee, a lake of the Swiss plateau, between 1848 and 1999.

Dated sediment cores provide an excellent way to investigate the historical input of persistent organic pollutants into the environment and to identify possible sources of pollution. The vertical distribution of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/F) and polychlorinated biphenyls (PCB) was investigated in a sediment core from Greifensee to elucidate the historical trends of PCDD/F and PCB inputs between 1848 and 1999. Concentrations of PCB and PCDD/F increased by more than one order of magnitude between 1930 and 1960. PCB and PCDD/F concentrations were 5700 ng/kg dry weight (dw) and 160 ng/kg dw, respectively, in sediments originating from the late 1930s and reached a maximum of 130,000 ng/kg dw and 2400 ng/kg dw, respectively, in the early 1960s. From 1960 on, concentrations decreased to the 1930s level by the mid 1980s. A remarkable shift in the PCDD/F pattern was observed after the early 1940s. Before 1940, the PCDD/F pattern was PCDF dominated (ratio of PCDD to PCDF=0.41+/-0.11), while the PCDD started to be the major species after the early 1940s (ratio of PCDD to PCDF=1.46+/-0.38). The temporal trends of PCB and PCDD/F correlate surprisingly well with each other. This might be due to the coincidence of two factors. The introduction of PCB on the market in the 1930s resulted in emissions due to the widespread use of these industrial chemicals. In the same time period, waste incineration became an increasingly popular way to get rid of garbage, boosting the PCDD/F emissions significantly. The rapid decline of PCDD/F and PCB concentrations in the sediment starting in the early 1960s reflects the result of better emission control techniques in thermal processes and the improvement of waste water treatment in the catchment of Greifensee.

Benzofurans↗
PubMed2007

Dose-dense chemotherapy for primary breast cancer.

PURPOSE OF REVIEW: Dose density is a relative term referring to the administration frequency of chemotherapy drugs and regimens compared with standard regimens. The concept of dose-dense chemotherapy is based on the hypothesis that maximal chemotherapy effectiveness can be achieved by scheduling the interval of chemotherapy to correspond to the period of most rapid tumor growth. The present paper aims to outline the theoretical framework for dose-dense chemotherapy and to review recent clinical trials addressing this concept within adjuvant breast cancer treatment. RECENT FINDINGS: Several randomized trials have been conducted to test the feasibility and effectiveness of anthracycline and/or taxanes-based dose-dense strategies. They demonstrate that using hematopoietic growth factor support has made dose-dense therapy safe and feasible. Dose-dense strategies have been associated with a modest impact on disease recurrence and overall survival of patients with early-stage breast cancer. Subset analyses suggest increased benefits for specific tumor subtypes such as hormone receptor-negative, highly proliferative or HER2 overexpressing tumors. SUMMARY: Trials in unselected patients with early-stage breast cancer have demonstrated promising results for dose-dense chemotherapy. Further studies are needed to define the optimal regimen and the patient population that will receive the greatest benefit from this therapy.

Antineoplastic Agents↗
PubMed2006

Biomarkers of depression in cancer patients.

BACKGROUND: Inflammation and perturbation of the hypothalamic-pituitary-adrenal (HPA) axis function appears to play a putative role in the etiology of depression. Patients with metastatic cancer demonstrate elevated prevalence rates for depression. The objective of the current study was to illustrate the efficacy of interleukin-6 (IL-6) and HPA axis function as adjuncts to support the diagnosis of depression in cancer patients. METHODS: Plasma concentrations of IL-6 and cortisol were measured in 114 cancer patients with and without depression. The relative diurnal variation of cortisol (cortisol VAR), expressed as a percentage, was calculated. Receiver operating characteristics analysis was performed. RESULTS: Depression was associated with increased plasma concentrations of IL-6 (18.7 pg/mL vs. 2.7 pg/mL; P < .001) and higher cortisol concentrations at 8 AM and 8 PM. The relative cortisol VAR (11.7% vs. 60.6%, respectively; P < .001) was found to be decreased in cancer patients with depression, indicating a disturbed circadian function of the HPA axis. As a biomarker of depression, IL-6 yielded at a cutoff value of 10.6 pg/mL, a sensitivity of 79%, and a specificity of 87% (area under the curve [AUC] = 0.86; 95% confidence interval [95% CI], 0.78-0.94), whereas cortisol VAR demonstrated a sensitivity of 81% and a specificity of 88% (AUC = 0.85; 95% CI, 0.74-0.97) at a cutoff value of 33.5%. CONCLUSIONS: Depression is associated with increased plasma IL-6 concentrations in patients with cancer. These patients demonstrate a dysfunction of the HPA-axis, characterized by a decreased diurnal variation of cortisol. The high sensitivity and specificity of these parameters biomarkers of depression make IL-6 and cortisol VAR helpful tools in the diagnosis of depression in patients with cancer.

Biomarkers, Tumor↗
PubMed2006

Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment.

PURPOSE: Malignant ovarian germ cell tumors are rare and knowledge about prognostic parameters currently is limited. This study was undertaken to evaluate long-term outcome of patients with malignant ovarian germ cell tumors (MOGCTs) after chemotherapy and to assess prognostic parameters. PATIENTS AND METHODS: A total of 113 patients with stage IC to IV MOGCTs were included into this retrospective study. Patients were treated at two large regional cancer centers between 1977 and 2003. RESULTS: Ten-year recurrence-free and overall survival rates were 82% and 81%, respectively. A total of 20 patients experienced relapse, all within the first 8 years. Outcome after relapse was poor, with only 10% of patients achieving long-term survival. Univariate and multivariate analyses demonstrated that initial stage of disease (relative risk [RR], 5.96; 95% CI, 3.47 to 10.22; P = .03) and elevation of serum markers beta-human chorionic gonadotropin and alpha-fetoprotein (RR, 3.90; 95% CI, 1.40 to 10.9; P = .009) were significant predictors of overall survival, whereas age at diagnosis was of no prognostic value. CONCLUSION: This is the first study to identify stage and tumor markers as prognostic parameters for patients with MOGCTs. This might help to select patients for risk-adapted treatment. There is need for improvement of therapeutic strategies after relapse.

Adolescent↗
PubMed2006

Occurrence of UV filters 4-methylbenzylidene camphor and octocrylene in fish from various Swiss rivers with inputs from wastewater treatment plants.

UV filters are widely used compounds in many personal care products and cosmetics, such as sunscreens. After use, UV filters are washed off from skin and clothes and enter the aquatic environment. Recent studies indicate that some lipophilic UV filters do accumulate in biota and act as endocrine disruptors. In this study, concentrations of 4-MBC (4-methylbenzylidene camphor) and OC (octocrylene), two widely used UV filters, were determined in the muscle tissue of fish (brown trout, Salmo trutta fario) from seven small Swiss rivers, all receiving inputs from wastewater treatment plants (WWTPs). Lipid-weight based concentrations of up to 1800 (4-MBC) and 2400 ng g(-1) (OC) were found. These levels were distinctly higher than those previously observed in white fish (Coregonus sp.) and roach (Rutilus rutilus) from Swiss lakes with inputs from WWTPs. This suggests a higher availability of these contaminants for fish in rivers than in lakes and identifies WWTPs as a major source for UV filters in the aquatic environment. As compared to lake fish, individual fish from a river showed much greater variation in 4-MBC and OC concentrations, likely as a result of a wider range of exposure in rivers than in lakes. 4-MBC concentrations correlated reasonably well with concentrations of methyl triclosan, a chemical marker for lipophilic WWTP-derived contaminants. The ratio P/Q of population (P) in a watershed to water throughflow (Q) is considered to be a measure of the domestic burden from WWTPs. A correlation of methyl triclosan with P/Q was previously observed with lake fish. However, such a correlation could not be confirmed with river fish. The higher average concentrations of OC as compared to 4-MBC in river fish, and the fact that OC was mostly absent in lake fish, suggests differences in bioaccumulation and availability of these two UV filters.

Acrylates↗
PubMed2006

Anaerobic degradation of brominated flame retardants in sewage sludge.

Tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and decabromodiphenyl ether (DecaBDE) are high production volume chemicals used as flame retardants in plastics for products such as electronic equipment, insulation panels, and textiles. The environmental safety of brominated flame retardants, especially their persistence, bioaccumulation, and toxicity is a controversial topic. Here, we studied and compared the degradation of TBBPA, HBCD, and DecaBDE under anaerobic conditions in digested sewage sludge. The half-lives of TBBPA and a technical HBCD mixture were 0.59 and 0.66 d, respectively. The fact that (+/-)-alpha-HBCD exhibited an almost doubled half-life compared to (+/-)-beta-HBCD and (+/-)-gamma-HBCD is an important finding with respect to the discussion on the persistence of individual HBCD stereoisomers and the recent reports on strong relative enrichment of alpha-HBCD in biota. We found no statistically significant enantioselective degradation of alpha-, beta-, or gamma-HBCD. Half-lives of TBBPA and a technical HBCD mixture were not dependent on the presence of additional nutrients or primers. Concentrations of TBBPA and a technical HBCD mixture decreased also in sterile control samples, however, at a rate that was more than a factor of 50 smaller than in incubations under non-sterile conditions. Compared to TBBPA and a technical HBCD mixture, DecaBDE exhibited a much longer half-life of 7 x 10(2)d in the same system. Pseudo-first-order degradation rate constants decreased according to the following sequence: TBBPA congruent with(+/-)-gamma-HBCD congruent with(+/-)-beta-HBCD>(+/-)-alpha-HBCD>>DecaBDE. Preliminary investigations suggest that degradation of TBBPA, HBCD, and DecaBDE occurs in full-scale anaerobic digesters, as well.

Anaerobiosis↗
PubMed2006

Three-dimensional fiber architecture of the nonpregnant human uterus determined ex vivo using magnetic resonance diffusion tensor imaging.

The global muscle and collagen fiber orientation in the human uterus has been analyzed hitherto by various standard microscopic techniques. However, no widely accepted model of the fiber architecture of the myometrium could be acquired. The purpose of the present study was to investigate the uterus by magnetic resonance (MR) diffusion tensor imaging (DTI) in a 3D macroscopic approach. Ex vivo MR DTI measurements were performed on five uteri from nonpregnant patients. The main diffusion directions reflecting the orientation of directional structures in the examined tissues were determined from diffusion-weighted spin-echo measurements. A fiber tracking algorithm was used to extrapolate the fiber architecture. The method was validated against histological slides and indirectly through the analysis of leiomyomas, which exhibit less anisotropy than normal myometrium. Significant anisotropy was found in most regions of all examined nonpregnant human uteri. But only two systems of fibers were found running circularly along the intramural part of the uterine tubes. They merged caudally and built a close fitting envelope of circular layers around the uterine cavity. On the cervix, circular fibers were observed in the outer part as well as mostly longitudinal fibers in the inner part. These results confirm the existence of directional structures in the complex fiber architecture of the human uterus. They also indicate that MR DTI is a beneficial and complementary tool to standard microscopic techniques to determine the intrinsic fiber architecture in human organs.

Adult↗
PubMed2006

Targeted transgene expression in neuronal precursors: watching young neurons in the old brain.

Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age-related neuronal loss and cognitive declines.

Age Factors↗
PubMed2006

Excimer laser versus narrow-band UVB (311 nm) in the treatment of psoriasis vulgaris.

BACKGROUND: The excimer laser is a new therapeutic option in the treatment of psoriasis vulgaris. OBJECTIVE: The purpose of this study was to determine the response of psoriasis lesions to the 308-nm excimer laser compared to 311-nm UVB phototherapy. METHODS: In this prospective right/left comparative, open, single-blinded trial, selected psoriasis plaques of 16 patients were treated with the excimer laser whereas the rest of the body was treated with UVB narrow-band phototherapy. A modified PASI score was used to evaluate the results. RESULTS: After 12 treatments, 15 patients were evaluated. In 2 patients no difference between the two body sides was observed. In 9 patients the laser-treated lesions showed better results, whereas in 4 patients the side treated with 311-nm UVB showed more clearing. The mean reduction in PASI score was 5.6 and 4.9, respectively (difference not significant). CONCLUSION: The use of the 308-nm xenon chloride excimer laser is an additional effective therapeutic option for the treatment of psoriasis vulgaris.

Adult↗
PubMed2006

Value of whole body 18FDG-PET to identify the active site of gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the usefulness of positron emission tomography with 18-fluorodeoxyglucose (18FDG-PET) in locating residual or relapsed gestational trophoblastic neoplasia (GTN). STUDY DESIGN: The Charing Cross GTN database was screened, and 11 patients who had undergone 18FDG-PET were identified. A retrospective analysis was conducted to determine the value of this investigation as compared with other imaging modalities in clinical care. RESULTS: All patients had elevated beta-human chorionic gonadotropin (beta-hCG) at the time of the investigation; none were false positive. In 7 patients the 18FDG-PET scans correctly confirmed the presence (4 of 7 cases) or absence (3 of 7 cases) of disease sites defined by other imaging investigations. In 2 patients positive PET-guided appropriate surgical resection of lung lesions that appeared of equivocal significance on computed tomography (CT) resulted in -hCG normalization. One patient had a pulmonary metastasis on CT not considered positive on 18FDG-PET (false negative). One patient with enlarged mediastinal lymph nodes on CT that were 18FDG-PET positive also had a vascular uterus on magnetic resonance imaging/Dopper ultrasound that was negative on PET (false negative). Hysterectomy led to hCG normalization and cure. The mediastinal lymph nodes were positive on CT and PET due to sarcoidosis (false positive). Patients with serum hCG levels <10 IU/L could have positive PET scans; that can contribute to patient care. CONCLUSION: 18FDG-PET can aid in identifying residual disease sites in women relapsing from previously treated GTN. However, careful evaluation in combination with other imaging modalities is required to reduce the risk of false positive and negative results.

Adult↗
PubMed2005

Gemcitabine as prolonged infusion and vinorelbine in anthracycline and/or taxane pretreated metastatic breast cancer: a phase II study.

BACKGROUND: Gemcitabine and vinorelbine are active agents for the treatment of metastatic breast cancer. Prolonged infusion of gemcitabine can result in higher levels of active metabolites compared to shorter administration. This phase II trial was initiated to evaluate the efficacy and tolerability of gemcitabine as prolonged infusion in combination with vinorelbine in anthracycline and/or taxane pretreated patients with metastatic breast cancer. PATIENTS AND METHODS: Patients who had received one prior line of chemotherapy for metastatic disease were treated with gemcitabine (350 mg/m2 as 4 h infusion) and vinorelbine (25 mg/m2 on days 1 and 8. Treatment was repeated every 3 weeks for a maximum of six cycles. RESULTS: Of 26 patients enrolled, 84% had received prior anthracycline treatment and 50% prior taxane therapy. In total, one complete and six partial responses were achieved, accounting for an overall response rate of 30.4%. The clinical benefit rate was 47.8%. Median duration of response and median time to progression were 7.3 months and 4.6 months, respectively. Median overall survival was 14.5 months. Although the predominant toxicity was myelosuppression with grade 3/4 neutropenia in 42% of patients, few neutropenic complications resulted. Non-hematological toxicity was generally moderate. Most common non-hematologic toxicities were nausea, vomiting, alopecia, peripheral neuropathy and elevation of liver enzymes. CONCLUSION: Gemcitabine as prolonged infusion and vinorelbine are a safe and effective combination treatment in anthracycline and/or taxane pretreated patients. Approximately 47.8% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving second-line therapy for metastatic breast cancer.

Adult↗
PubMed2005

Joint sealants: an overlooked diffuse source of polychlorinated biphenyls in buildings.

In October 2000, joint sealants containing polychlorinated biphenyls (PCB) were discovered in various public buildings in Switzerland. Triggered by this event, a nationwide comprehensive study was initiated by the Swiss Agency for the Environment, Forests, and Landscape, and 1348 samples of joint sealants as well as 160 indoor air samples from concrete buildings erected between 1950 and 1980 were analyzed. Out of 1348 samples, 646 (48%) contained PCB. In 279 (21%) samples, PCB concentrations of 10 g/kg and more were detected, and concentrations of 100 g/kg of PCB or more were found in 129 (9.6%) samples. These data indicate that PCB were widely used as plasticizers in joint sealants in Switzerland. In buildings constructed between 1966 and 1971, one-third of all joint sealants investigated contained more than 10 g/kg of PCB. PCB concentrations exceeding the limit of 0.050 g/kg above which material is required to be treated as PCB bulk product waste were reached by 568 samples (42%). PCB with a chlorine content between 45 and 55%, corresponding to mixtures such as Clophen A50, Aroclor 1248, and Aroclor 1254, were encountered in 316 samples (70%). In 42 cases (26%) where joint sealants containing PCB were present, clearly elevated PCB indoor air concentrations above 1 microg/m3 were encountered. In eight cases (5%), levels were higher than 3 microg/m3. The Swiss tentative guideline value of 6 microg/m3 (based on a daily exposure of 8 h) for PCB in indoor air was exceeded in one case (0.6%). On the basis of this work, representing the first large-scale nationwide analysis of the issue of PCB-contaminated joint sealants, we estimate that there are still 50-150 t of PCB present in these materials, acting as diffuse sources. They are distributed over many hundreds of buildings all over the country and represent a significant but frequently overlooked inventory of PCB. In light of the Stockholm Convention on persistent organic pollutants that entered into force last year, reduction of the release of PCB from these widely used materials is an important issue to be addressed.

Air Pollutants, Occupational↗
PubMed2005

Anaerobic degradation of decabromodiphenyl ether.

The environmental safety of decabromodiphenyl ether (BDE-209), a widely used flame retardant, has been the topic of controversial discussions during the past several years. Degradation of BDE-209 into lower brominated diphenyl ether congeners, exhibiting a higher bioaccumulation potential, has been a critical issue. Here, we report on the degradation of BDE-209 and the formation of octa- and nonabromodiphenyl ether congeners under anaerobic conditions. Sewage sludge collected from a mesophilic digester was used as the inoculum and incubated up to 238 days with and without a set of five primers. Following Soxhlet extraction and a liquid chromatography cleanup procedure, parent compounds and debromination products were analyzed by GC/HRMS. In experiments with primers, concentrations of BDE-209 decreased by 30% within 238 days. This corresponds to a pseudo-first-order degradation rate constant of 1 x 10(-3) d(-1). Without primers, the degradation rate constant was 50% lower. Formation of two nonabromodiphenyl ether and six octabromodiphenyl ether congeners proved that BDE-209 underwent reductive debromination in these experiments. Debromination occurred at the para and the meta positions, whereas debromination at the ortho position was not statistically significant. All three nonabromodiphenyl ether congeners (BDE-206, BDE-207, and BDE-208) were found to undergo reductive debromination as well. No significant change of the BDE-209 concentration and no formation of lower brominated congeners was observed in sterile control experiments. To our knowledge, this is the first report demonstrating microbially mediated reductive debromination of BDE-209 under anaerobic conditions.

Animals↗
PubMed2005

Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.

PURPOSE: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. RESULTS: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. CONCLUSION: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.

Adult↗