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C Bokemeyer

Publications and source records attributed to C Bokemeyer.

At least 19 recordsLinked to original sources

A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in 80%-90% of non-small-cell lung cancer (NSCLC). Matuzumab, a humanized immunoglobulin G(1) (IgG(1)) anti-EGFR monoclonal antibody, blocks activation of EGFR. Paclitaxel and EGFR inhibitors have additive antitumour effects in vitro. This phase I study assessed the tolerability, pharmacokinetics and efficacy of the combination of matuzumab and paclitaxel in patients with advanced NSCLC. MATERIALS AND METHODS: Eighteen chemotherapy-naïve (n = 9) or pretreated (n = 9) patients with stage IIIB or IV EGFR-positive NSCLC received weekly doses of matuzumab (100, 200, 400 or 800 mg) followed by paclitaxel 175 mg/m(2) every 3 weeks. Toxicity was evaluated weekly and pharmacokinetics were measured during cycles 1 and 2. RESULTS: The maximum planned matuzumab dose of 800 mg was achieved without reaching the maximum tolerated dose. Grade 4 neutropenia occurred in one of three patients at 800 mg but resolved within 1 week; five additional patients treated with 800 mg had no dose-limiting toxicity (DLT). Grade 1/2 acneiform skin rash in 14 patients was the most frequent matuzumab-related side-effect. There were no higher-grade adverse events. Grade 2 toxicities included pruritus (n = 2), bronchospasm (n = 1), fissures (n = 1), abdominal pain (n = 1) and hot flushes (n = 1). Paclitaxel was discontinued in four patients due to allergic reactions. Coadministration of paclitaxel did not alter matuzumab pharmacokinetics. Responses occurred in four of 18 patients and included one complete response. CONCLUSIONS: Matuzumab doses up to 800 mg weekly with paclitaxel 175 mg/m(2) every 3 weeks are well tolerated, with no apparent drug interactions and with evidence of antitumor activity.

Adult↗

An open label, non-comparative phase II study of gemcitabine as salvage treatment for patients with pretreated adult type soft tissue sarcoma.

BACKGROUND: The number of effective cytotoxic agents for the treatment of patients with metastatic adult type soft tissue sarcoma (STS) is limited, when patients have failed anthracyline-based chemotherapy. The aim of this trial was to evaluate the efficacy of gemcitabine in this setting. METHODS: Between August 2001 and March 2003 19 patients were eligible to enter. Gemcitabine was administered as a 30-minutes infusion at a dosage of 1 g/m2 on day 1, 8 and 15 every 4 weeks. All patients had progressive disease during (n = 12) or shortly after an anthracycline-based regimen (n = 3). RESULTS: Four of 19 patients did not start study treatment because of fulminant progression. Fifteen patients with a median age 47 years (32-72) were assessable. All patients had received at least one prior treatment regimen (range, 1-6) for metastatic disease containing anthracyclines (n = 15) and ifosfamide (n = 11). To date, a total of 72+ cycles have been applied (median; 3, 1-28+). Seven patients (47%) had progressive disease after completion of two cycles at the first response assessment. One patient (6%) attained a partial remission, and 7 patients (47%) achieved disease stabilisations. One patient is still on treatment after more than 2.5 years. The calculated progression-free rate at 3 and 6 months was 46.7% (CI(95%), 21.4-71.9) and 13.3% (CI(95%), (0-30.5). 95% of the cycles have been applied without any dose modification or treatment delay. CONCLUSIONS: Considering response and progression-free rate as the primary endpoints for phase II trials in pretreated STS, gemcitabine has moderate efficacy.

Adult↗

A multi-center phase II study of BMS-247550 (Ixabepilone) by two schedules in patients with metastatic gastric adenocarcinoma previously treated with a taxane.

PURPOSE: Ixabepilone is one of the epothilones, a new class of cytotoxics, that function as microtubule-stabilizing agents. With the primary endpoint of assessing ixabepilone's response rate against metastatic gastric cancer previously treated with a taxane, we performed a multi-center phase II trial. PATIENTS AND METHODS: Patients with histologically documented metastatic gastric or gastroesophageal adenocarcinoma, who had previously received a taxane, were eligible. Patients were required to have near normal organ function, > or =18 years of age, ECOG performance status of 0 or 1. A written informed consent was obtained from all patients. Ixabepilone was administered over one hour intravenously at a dose of 50 mg/m2 every 21 days (23 patients; cohort A) and 24 subsequent patients were treated with an amended protocol schedule to receive 6 mg/m2 intravenously on days 1-5 every 21 days (cohort B). RESULTS: A total of 47 patients were treated. Most patients were men with a median performance status of 1. Two of 23 patients in cohort A achieved a confirmed partial response (9%, 95% CI 1.1-28%) but none of the 24 patients in cohort B achieved a response. A higher proportion of patients in cohort A experienced Grade 3/4 toxicities compared with those in cohort B. CONCLUSIONS: Ixabepilone, on a once every 21-day schedule, is modestly active against metastatic gastric cancer previously treated with a taxane. The days 1-5 every 21 days schedule had a more favorable safety profile but no activity. The results of this study suggest that once every 21-day ixabepilone schedule should be pursued further in untreated gastric or gastroesophageal adenocarcinoma patients.

Adenocarcinoma↗

Experimental metastasis and primary tumor growth in mice with hemophilia A.

During experimental lung metastasis, tumor cells adhere to the pulmonary microvasculature and activate coagulation via surface-expressed tissue factor (TF), leading to local fibrin deposition and platelet aggregation. While interventional studies have demonstrated great efficacy of anticoagulants and antiplatelet agents in inhibiting metastasis, no information is available on how tumor biology may be affected by congenital bleeding disorders such as hemophilia A. We therefore used a syngeneic model to study experimental metastasis and primary tumor growth in factor VIII (FVIII)-deficient mice. By conventional reverse transcription-polymerase chain reaction, flow cytometry, and one-stage clotting assays, we demonstrated constitutive expression of TF mRNA, antigen, and procoagulant activity in the murine B16F10 melanoma cell line. In hemophilic mice, B16F10 lung metastasis was significantly (P < 0.001) enhanced by a single dose of human FVIII (100 U kg(-1)), suggesting that FVIII played a critical role during the early blood-borne phase of the metastatic cascade. In contrast, lung seeding was significantly (P < 0.05) reduced by lepirudin, a direct thrombin inhibitor, suggesting that thrombin generation contributed to pulmonary metastasis even in the absence of FVIII. Consistent with this finding, intravenous injection of B16F10 cell-evoked laboratory changes of a hemolytic thrombotic microangiopathy and consumptive coagulopathy in both hemophilic and non-hemophilic mice. Subcutaneous implantation of B16F10 cells into mice with hemophilia A gave rise to primary tumors in an exponential growth pattern similar to that observed in non-hemophilic mice. Although TF expression by B16F10 cells may promote thrombin-dependent metastasis in mice with hemophilia A, amplification of coagulation by host FVIII appears to be necessary for maximum lung seeding.

Animals↗

Correlation of bFGF expression in renal cell cancer with clinical and histopathological features by tissue microarray analysis and measurement of serum levels.

The prognostic value of bFGF for surgically treated renal cell cancer (RCC) patients was evaluated by immunohistochemistry (IHC) and the tissue microarray technique (TMA). Additionally, preoperative serum bFGF levels were correlated to tumour stage and the presence of metastases at initial diagnosis. Serum levels of bFGF were measured by ELISA in 39 healthy volunteers, in 37 patients with benign urologic diseases and in 74 RCC patients, 26 of whom revealed lymph node or distant metastases. bFGF expression as detected by IHC was investigated in 777 tissue cores from 259 different RCC patients [median follow-up: 138 (36-240) months]. Eighty eight patients died from tumour progression. For each patient, the TMA slides contained a tissue core from the primary tumour, its invasion front and the normal renal parenchyma. bFGF serum levels were higher in RCC patients vs healthy volunteers (P<0.01) and vs patients with benign urologic diseases (P<0.01). Metastasized patients revealed higher bFGF serum levels than organ-confined specimens (P<0.01). As detected by IHC only increased bFGF expression in the invasion front tissue correlated with the patients' long-term survival (log rank test) (P=0.03). In multivariate analysis regional LN metastases (P<0.01), the histological grading (P<0.01), and an increased bFGF expression in the invasion front (P=0.04) independently predicted the patients' clinical prognosis. Not the expression of bFGF in the primary tumour but in its invasion front reflects the aggressiveness of RCC, hereby indicating a different biological potential within both areas. The value of bFGF serum levels as indicators of systemic tumour dissemination remains to be determined.

Adult↗

Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.

PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU 2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214). RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.

Adult↗

Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO.

BACKGROUND: The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy. PATIENTS AND METHODS: Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 h was scheduled in between the two cycles. RESULTS: Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(M0) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3-25) for FLP and 18 months (2-51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% CI 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group. CONCLUSIONS: Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.

Adenocarcinoma↗

Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study.

BACKGROUND: In the development of the human ovary, the second trimester includes the transition from oogonial replication to primordial follicle formation. The present study was carried out to assess differentiation and proliferation of germ cells in a series of female gonads from 19 fetuses from the second and third trimester, and two neonates. METHODS: Using immunohistochemistry, the following markers were studied: placental/germ-like cell alkaline phosphatases (PLAP), the marker of pluripotency OCT3/4, the proliferation marker Ki-67, beta-catenin and E-cadherin, the stem cell factor receptor c-KIT, and VASA, a protein specific for the germ cell lineage. RESULTS: PLAP and OCT3/4 were seen during oogenesis, but not in germ cells engaged in folliculogenesis. A similar pattern was observed for Ki-67. Loss of pluripotency occurs once oocytes engage in follicle formation, suggesting a role of cell-cell interactions in the process of germ cell maturation. VASA, c-KIT, beta-catenin and E-cadherin were found in germ cells at all developmental stages of oogenesis and folliculogenesis. CONCLUSIONS: Immunohistochemically, two groups of germ cells can be distinguished. Germ cells that are predominantly found in the cortical region of the ovary before weeks 22-24 of gestation, showing an immature phenotype, are mitotically active, and express OCT3/4, a marker of pluripotency. On the other hand, germ cells undergoing folliculogenesis have lost their pluripotent potential and no longer proliferate.

Alkaline Phosphatase↗

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Adult↗

[Compression syndromes].

Superior vena cava syndrome is a medical condition determined by the mechanisms of extrinsic compression, invasion or thrombosis of the superior vena cava. The most common underlying cause is a malignant process, especially lung cancer and lymphoma. Typical symptoms include progressive dyspnea, head and upper body edema and cyanosis. Most patients can be treated with appropriately directed chemotherapy or radiotherapy. Accurate diagnosis of the underlying etiology needs to be established before treatment. Only under extreme emergency conditions such as laryngeal or cerebral edema irradiation should be initiated without a histological diagnosis. With the refinement of endovascular stents, percutaneous stenting is being increasingly used as primary treatment modality. Metastatic spinal cord compression is one of the most dreadful complications of cancer. In most patients the initial symptom is progressive back pain with an axial or radicular distribution. MRI should be preferred in the diagnostic work-up, corticosteroids be administered promptly after biopsy. Radiation therapy or surgical treatment should be started as soon as possible.

Acute Disease↗

Antiangiogenic treatment with endostatin inhibits progression of AML in vivo.

Increased vessel density in the bone marrow of patients with acute myeloid leukemia as well as elevated expression of proangiogenic factors by leukemic cells implies a central role of angiogenesis in hematological malignancies. Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of angiogenesis that has shown therapeutic activity in solid tumors in various preclinical models. Using microencapsulation technology, we studied the therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 murine leukemic cells in vitro, ES producing microbeads significantly inhibited growth of subcutaneous chloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with ES microbeads prolonged median survival significantly. Histological analysis revealed a decreased microvessel density and a reduced number of CD31-positive single cells, putatively endothelial progenitor cells, in the bone marrow of treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis in the bone marrow and on progression of leukemia in vivo. These experiments suggest a possible therapeutic role of antiangiogenic gene therapy with ES in AML.

Acute Disease↗

Anaemia in cancer patients: pathophysiology, incidence and treatment.

This review focuses on the pathophysiology, incidence and treatment of anaemia in cancer patients. Causative factors such as different chemotherapy regimens and patient risk factors for the development of anaemia are discussed in order to identify the patient group that is most likely to receive red blood cell transfusions and would thus have the largest benefit from treatment with erythropoietic proteins. The data available with recombinant human erythropoietin alfa, recombinant human erythropoietin beta and darbepoetin alfa are described in more detail and the significant benefit of treating cancer anaemia by these molecules is outlined. Finally, differences in treatment approaches between these erythropoietic proteins are discussed in order to guide treatment decisions specific for the individual patients' situation.

Anemia↗

Secondary leukemia after first-line high-dose chemotherapy for patients with advanced germ cell cancer.

PURPOSE: We investigated the incidence of secondary leukemia in patients treated with first-line high-dose chemotherapy (HDCT) plus autologous stem cell transplantation (PBSCT) for advanced testicular cancer. METHODS: Three hundred and twenty-three patients who were entered into two consecutive prospective Phase-II studies of the German Testicular Cancer Study Group were analyzed. A total of 221 patients had received HD-VIP containing cisplatin, ifosfamide, and etoposide and 102 patients were treated with Tax-HD-VIP containing cisplatin, ifosfamide, etoposide, and paclitaxel, each cycle supported by autologous PBSCT. RESULTS: Patients had received a median cumulative etoposide dose of 4.9 g/m(2) (range, 2.2-9.4 g/m(2)). The median follow-up duration for all patients was 36 months (range, 0-128) with a median follow up time of 50 months (range, 0-128) for patients surviving at least 1 year after therapy. One patient developed a secondary acute myeloid leukemia (s-AML) involving a chromosomal translocation t(11;19)(q23;p13.3) 24 months after the start of chemotherapy resulting in a cumulative incidence of 0.48% [95% confidence interval (CI) 0-1.42]. Additionally, two patients with primary mediastinal germ cell cancer developed a myelodysplastic syndrome. No solid tumors had occurred. CONCLUSIONS: HDCT including high-dose etoposide with autologous PBSCT as first-line therapy for advanced testicular cancer was associated with an acceptably low risk of developing secondary leukemia.

Antineoplastic Combined Chemotherapy Protocols↗

Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer.

PURPOSE: To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). PATIENTS AND METHODS: Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. RESULTS: Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. CONCLUSION: Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.

Antineoplastic Combined Chemotherapy Protocols↗

Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial.

The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice daily on days 1-14 plus i.v. bolus mitomycin C on day 1 at doses of 4, 6, 8 or 10 mg m(-2) (corresponding to dose levels I-IV). Cycles were repeated every 3 weeks. Two treatment cycles were considered for the evaluation of DLTs. Of the 53 patients enrolled, the majority had colorectal (n=27) or gastric (n=14) cancers. Patients had received a median of two lines of prior chemotherapy (34% with >/=3 lines and 87% with prior 5-FU-based therapy). At the recommended dose level (IV, n=30), grade 3 adverse events during cycles 1 and 2 were: anaemia (10%); leukopenia (3%); thrombocytopenia (3%); stomatitis/mucositis (3%); hand-foot syndrome (3%). Two patients experienced DLTs (mucositis, n=1; neutropenic fever, n=1), but there were no grade 4 events. The median dose intensity for capecitabine and mitomycin C was 100% during cycles 1 and 2 and only four patients required postponement of therapy. Of the 43 patients evaluable for efficacy, seven achieved partial and minor remissions (16%; 95% CI, 5-28%), and 12 patients (28%) had stable disease. The favourable safety profile and promising activity of the capecitabine/mitomycin C combination, even in heavily pretreated patients, warrant further evaluation in patients with advanced colorectal and gastric cancers.

Adult↗

Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials.

To study the role of single agent carboplatin chemotherapy in patients with metastatic seminoma based on the data from two randomised trials. In subgroup analyses in patients with different disease characteristics, the outcome treated with either single agent carboplatin or cisplatin-based combination chemotherapy was compared. Individual patient data from two randomised European trials involving patients with metastatic seminoma were gathered. The primary endpoint for all analyses was progression-free survival. The source data of 361 patients, 184 treated with cisplatin-based combinations and 177 treated with carboplatin single agent therapy, were entered into the analysis. Patient characteristics were comparable among the cisplatin-based and the carboplatin single agent treated patient groups with lymph nodes and lungs being the most frequent metastatic sites in 92 and 8% of patients, respectively. Overall, patients treated with single agent carboplatin had an inferior 5-year overall (89 and 94%; P=0.09) and progression-free survival rate (72 and 92%; P< 0.0001) compared with patients receiving cisplatin-based combinations. For all investigated subgroups (based on age, prior radiation therapy, metastatic sites), carboplatin single agent therapy was found to be inferior to cisplatin-based combination chemotherapy. In conclusion, carboplatin single agent therapy cannot be recommended as standard treatment for any patient subgroup with advanced metastatic seminoma and cisplatin-based combination regimens remain the standard of care.

Adolescent↗