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1.
Br J Cancer ; 124(4): 721-727, 2021 02.
Article in English | MEDLINE | ID: mdl-33235314

ABSTRACT

BACKGROUND: Patients with carcinoma of unknown primary (CUP) have a dismal prognosis, even when treated with multi-agent chemotherapy. We hypothesised that adding the epidermal growth-factor receptor (EGFR) inhibitor cetuximab to standard first-line chemotherapy with paclitaxel and carboplatin would improve PFS and RR in unfavourable CUP. METHODS: This open-labelled, multicentre Phase 2 study included patients with unfavourable, untreated adeno- or undifferentiated CUP. Patients were randomised to receive either paclitaxel/carboplatin (group A) or paclitaxel/carboplatin plus cetuximab (group B) every 3 weeks for a maximum of 6 cycles followed by cetuximab maintenance in group B. The primary endpoint was PFS in the two groups. Secondary endpoints were RR, toxicity and overall survival (OS). RESULTS: One-hundred-and-fifty patients were randomised (group A = 72, group B = 78). The median PFS and OS for all patients were 3.8 and 8.1 months (95% confidence interval (CI): 2.9-4.8 and 6.8-9.5). There was no significant difference in PFS (3.7 vs 4.6 months, HR 0.98) or OS (8.1 vs 7.4, HR 1.1) between the two treatment groups. Response rate tended to be better for chemotherapy plus cetuximab compared to chemotherapy alone (22% vs 15%). Adverse events grade ≥3 were comparable between the two groups, except for significantly increased skin toxicity in the cetuximab arm. CONCLUSIONS: Cetuximab plus paclitaxel/carboplatin did not improve PFS, OS and RR in metastatic CUP compared to paclitaxel/carboplatin alone. Addition of cetuximab resulted in additional skin toxicity. CLINICAL TRIAL REGISTRATION: The study was registered at clinicaltrials.gov as NCT00894569.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Unknown Primary/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Cetuximab/administration & dosage , Cetuximab/adverse effects , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Progression-Free Survival , Survival Rate
2.
Virchows Arch ; 456(1): 23-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20012089

ABSTRACT

For the clinical diagnosis and appropriate therapy of patients with cancer of unknown primary (CUP), biopsies of the tumor metastases are generally examined histopathologically and by immunohistochemistry (IHC). Gene expression profiling (GEP) is a new diagnostic technique that might further contribute to tumor specification. Biopsies of 43 CUP cases underwent a retrospective central histopathological and immunohistochemical review and centrally performed GEP using CupPrint(TM). Two samples could not be evaluated by IHC due to small biopsy size or loss of immunoreactivity. One of these and 17 other samples were not suited for GEP due to RNA degradation. In 13 out of the remaining 24 cases (54%), the same primary was proposed by IHC and GEP and was supported by the clinical findings, furthermore leading to the doubtless identification of the primary in four out of these. In seven cases, there was discordance between IHC and GEP, with the clinical picture being more in line with IHC in three and with GEP in four cases. Four cases had to remain undecided because the primary tumors suggested by IHC and GEP were not supported. In conclusion, overlap between IHC and GEP results and the clinical presentation was noted in the majority of those true CUP cases that were evaluable with both techniques. Therefore, GEP can be a complementary diagnostic technique assisting immunohistochemical profiling of cancer biopsies with unknown primary.


Subject(s)
Gene Expression Profiling/methods , Immunohistochemistry/methods , Neoplasm Metastasis/genetics , Neoplasms, Unknown Primary/genetics , Female , Humans , Male , Middle Aged
3.
Onkologie ; 32(4): 162-6, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19372710

ABSTRACT

BACKGROUND: Carcinomas of unknown primary (CUP) account for approximately 2-5% of all cancer diagnoses. Except for some subsets with favorable prognosis, for most of these patients treatment options are limited, and no standard first-line regimen has been identified. We performed a phase II study with oxaliplatin (OX) and capecitabine (CAP) as first-line treatment for patients with histo-or cytologically proven adeno- or undifferentiated CUP. PATIENTS AND METHODS: Protocol treatment in this multicenter trial consisted of CAP 1,000 mg/m(2) twice daily orally (days 1-14) and OX 130 mg/m(2) intravenously (day 1), repeated every 21 days at a maximum of 6 cycles. The primary endpoint was the response rate (RR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 51 patients with CUP (71% with poorly differentiated adenocarcinoma; 41% ECOG performance status (PS) 0, 39% PS 1, 10% PS 2, 55% with elevated lactate dehydrogenase (LDH), and 39% with liver metastases) were enrolled in this study. We observed an objective RR of 11.7% and a median PFS of 2.5 months as well as an OS of 7.5 months with a good toxicity profile. CONCLUSION: CAP/OX did not reach higher RR compared to a standard regimen with paclitaxel/carboplatin, which discourages further investigation of this schedule in CUP.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoplasms, Unknown Primary/drug therapy , Organoplatinum Compounds/administration & dosage , Adenocarcinoma/diagnosis , Adult , Aged , Capecitabine , Deoxycytidine/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasms, Unknown Primary/classification , Neoplasms, Unknown Primary/diagnosis , Oxaliplatin , Treatment Outcome
4.
J Clin Oncol ; 23(3): 432-40, 2005 Jan 20.
Article in English | MEDLINE | ID: mdl-15659490

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Disease Progression , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Infusions, Intravenous , Middle Aged , Mitoxantrone/administration & dosage , Paclitaxel/administration & dosage , Peripheral Blood Stem Cell Transplantation , Quality of Life , Survival Analysis , Treatment Outcome
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