Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma?

Lenzi, Renato; Hess, Kenneth R.; Abbruzzese, Marie C.; Raber, Martin N.; Ordonez, N.; Abbruzzese, James L.

doi:10.1200/jco.1997.15.5.2056

Cited by 82 publications

(23 citation statements)

References 17 publications

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“…For the minority of tumours that have been identified in the last two decades as being potentially sensitive to chemotherapy (van der Gaast et al, 1990;Pavlidis et al, 1992;Abbruzzese et al, 1995;Lenzi et al, 1997;Greco and Hainsworth, 2001b), the diagnostic procedures will delay these patients from receiving effective treatment.…”

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Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

et al. 2004

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The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m À2 day 1, doxorubicin 50 mg m À2 day 1, etoposide 100 mg m À2 days 1 -3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2 -36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III -IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

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Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

et al. 2004

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“…These include: (i) peritoneal carcinomatosis or malignant ascites in women, particularly with serous cancers where ovarian cancer protocols are often effective, (ii) women with axillary lymph node metastases where treatment for occult breast carcinoma has been shown to be effective, (iii) male patients with osteoblastic bone metastases where empiric hormonal manipulation for metastatic prostate cancer would seem worthwhile, (iv) young males with undifferentiated carcinomas, involving retroperitoneal mediastinal lymph nodes where empirical treatment for germ cell tumour may be appropriate, (v) patients who present with metastatic squamous cell carcinoma in high cervical nodes where radical treatment for head and neck cancer is usually undertaken (Lenzi et al, 1997).…”

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Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study

et al. 2006

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Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0 -2 were treated with G 1000 mg m À2 intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41 -83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3 -4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP.

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“…7) Similarly, Currow et al found that only 2 of 9 patients in whom β-HCG was elevated to more than 8 times the upper normal limit responded to platinum-based chemotherapy. 13) Although the number of patients was small in the present study, significant elevation of β-HCG (>10 mIU/ml; that is, more than 20 times the upper normal limit), might suggest a better response to platinum-based chemotherapy.…”

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confidence: 99%

Treatable Subsets in Cancer of Unknown Primary Origin

Sumi

Itoh

Onozawa

et al. 2001

Japanese Journal of Cancer Research

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The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1-50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom β β β β-subunit of human chorionic gonadotropin (β β β β-HCG) was elevated more than 10 mIU/ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of β β β β-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.Key words: Cancer of unknown primary -Chemotherapy -Chemosensitive subgroups -β-HCGThe development of imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging, has enabled the detection of the site of primary cancers, as well as metastatic sites. Moreover, immunohistochemical studies were introduced into routine clinical oncology practice recently and have significantly increased the probability of identifying the likely underlying tumor type.1) In spite of these notable advances, the primary site of cancer can still not be determined in approximately 5-10% of all cancer patients.2) As a result, these patients are diagnosed as having "cancer of unknown primary" site (CUP). Accordingly, CUP, by its nature, is extremely heterogeneous in clinical presentation, histologic appearance, and natural history, and there is no standard treatment for CUP. Although reports of patients with CUP have indicated poor prognosis, with overall survival duration of 5-11 months from diagnosis of CUP, [3][4][5] several favorable prognostic factors for chemotherapeutic response have been proposed and the treatment results of patients with such factors were markedly better. 6) However, there is very little information concerning Japanese patients with CUP.To establish such treatable subsets and to identify further prognostic factors predictive of positive responses to chemotherapy, Japanese patients with CUP were retrospectively analyzed after appropriate clinical and pathological exclusion of primary tumors, according to current diagnostic recommendations.

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Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown origin: favorable subsets of patients with unknown-primary carcinoma?

Cited by 82 publications

References 17 publications

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study

Treatable Subsets in Cancer of Unknown Primary Origin

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