Fluorouracil plus Folinic Acid in Metastatic Adenocarcinoma of Unknown Primary Site Suggestive of a Gastrointestinal Primary

1993 ◽  
Vol 79 (2) ◽  
pp. 116-118 ◽  
Author(s):  
Franco Nolè ◽  
Marco Colleoni ◽  
Roberto Buzzoni ◽  
Emilio Bajetta
Keyword(s):  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
Treatment Strategies ◽  
Unknown Primary ◽  
Severe Diarrhea ◽  
Results Of Treatment ◽  
Ca 19.9 ◽  
Primary Location ◽  
Primary Origin

Aims and Background The results of treatment strategies for carcinoma of an unknown primary location have been discouraging. Currently, no chemotherapeutic approach can be considered standard. Methods We therefore initiated a Phase II study in which fluorouracil (370 mg/m2, day 1 through 5) plus folinic acid (200 mg/m2 day 1 through 5) was administered in a subset of 17 patients (median age, 57 years) affected by histologically diagnosed adenocarcinoma of unknown primary location characterized by liver metastases and elevated CEA of CA 19.9. All of the patients had a performance status of 0-2 (ECOG Scale), and liver involvement was > 30 % in 7 cases. Results No objective response was observed (4 cases of stabilization and 13 of disease progression). Median survival was 5 months. Toxicity was mild or moderate, and severe diarrhea was observed in only one case. Conclusions The proposed regimen is inactive among this subset of patients and confirms that subdiaphragmatic metastases are related to a poor prognosis. Our results, in agreement with data published in the literature, suggest that patients affected by adenocarcinoma of an unknown primary origin metastatic to the liver and with a good performance status should be treated in an investigative setting.

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

Reversal of Resistance to Doxifluridine and Fluorouracil in Metastatic Colorectal Cancer: The Role of High-Dose Folinic Acid

1992 ◽  
Vol 78 (4) ◽  
pp. 258-261 ◽  
Author(s):  
Marco Colleoni ◽  
Emilio Bajetta ◽  
Filippo de Braud ◽  
Nicoletta Zilembo ◽  
Franco Noiè ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Colon And Rectum

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) dally for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridlne, a new fluoropyrimldine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64 %), lung (35 %), local recurrence (10 %) and peritoneum (10 %). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxlfluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

Evaluation and Management of the Unknown Primary Carcinoma of the Head and Neck

2008 ◽  
Vol 6 (10) ◽  
pp. 1068-1075 ◽  
Author(s):  
Chad E. Galer ◽  
Merrill S. Kies
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Clinical Presentation ◽  
Treatment Strategies ◽  
Clinical Problem ◽  
Unknown Primary ◽  
Multidisciplinary Teams ◽  
Primary Origin ◽  
Unknown Primary Carcinoma

Squamous cell carcinoma of unknown primary origin in the head and neck is encountered as a recurring clinical problem in head and neck cancer clinics, affecting 3% to 25% of patients. This article describes the clinical presentation, appropriate evaluation, and treatment strategies for this important subgroup. Treatment—best carried out with multidisciplinary teams of specialists experienced in the care of head and neck cancer patients—is curative for most of these patients.

Prognostic factors in metastatic carcinoma of unknown primary.

1986 ◽  
Vol 4 (11) ◽  
pp. 1652-1657 ◽  
Author(s):  
R Pasterz ◽  
N Savaraj ◽  
M Burgess
Keyword(s):  
Prognostic Factors ◽  
Median Survival ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Objective Response ◽  
Metastatic Carcinoma ◽  
Unknown Primary ◽  
Carcinoma Of Unknown Primary ◽  
Good Performance Status ◽  
Metastatic Sites

From January 1980 to June 1984, 70 patients with metastatic carcinoma of unknown primary treated with combination chemotherapy were analyzed for prognostic factors influencing objective response and survival. Suspicious germ-cell tumors and neuroendocrine tumors were excluded since patients with these malignancies tend to live longer than those with metastatic carcinoma of unknown primary. Objective response rate to combination chemotherapy was 28%. Median survival of all patients responding to combination chemotherapy was better than those not responding (16 v 3 months). In patients with good performance status, median survival was longer in responders than nonresponding patients (17 v 7 months). External lymph nodes or subcutaneous disease as the only site of disease and good performance status favorably influenced both objective response and survival, while the number of different metastatic sites favorably influenced only survival. Neutropenia and thrombocytopenia were appreciable but not fatal or a great cause of morbidity in those with good performance status. Thus, patients with metastatic carcinoma of unknown primary with good performance status or only external nodes or subcutaneous disease should be treated with combination chemotherapy regardless of age, histology, or number of different metastatic sites of disease.

Phase II study of cisplatin, 5-fluorouracil and folinic acid in patients with carcinoma of unknown primary origin

1993 ◽  
Vol 29 (11) ◽  
pp. 1634 ◽  
Author(s):  
Renato Lenzi ◽  
Martin N. Raber ◽  
Philip Frost ◽  
Susan Schmidt ◽  
James L. Abbruzzese
Keyword(s):  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Unknown Primary ◽  
Carcinoma Of Unknown Primary ◽  
Primary Origin ◽  
Unknown Primary Origin

Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin

2020 ◽  
Vol 44 (4) ◽  
Author(s):  
Krystallenia I. Alexandraki ◽  
Marina Tsoli ◽  
Georgios Kyriakopoulos ◽  
Anna Angelousi ◽  
Georgios Nikolopoulos ◽  
...  
Keyword(s):  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Diagnosis And Management ◽  
Primary Origin ◽  
Unknown Primary Origin

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

scholarly journals Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival

2020 ◽  
Author(s):  
Lars Axelsson ◽  
Erik Holmberg ◽  
Jan Nyman ◽  
Anders Högmo ◽  
Helena Sjödin ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Prognostic Factors ◽  
Head And Neck ◽  
Neck Dissection ◽  
Neck Cancer ◽  
Multicenter Study ◽  
Performance Status ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
N Stage

Abstract Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p= 0.036), and N stage (p= 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment.

scholarly journals Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Poor Performance Status ◽  
Poor Overall Survival ◽  
Melanoma Brain Metastases

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

Sign in / Sign up

Export Citation Format

Share Document