Paclitaxel/carboplatin plus bevacizumab/erlotinib in the first-line treatment of patients with carcinoma of unknown primary site.
BACKGROUND
This phase II trial evaluated the efficacy and toxicity of the combination of paclitaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with carcinoma of unknown primary site (CUP).


METHODS
Patients with previously untreated CUP (adenocarcinoma, poorly differentiated carcinoma, poorly differentiated squamous carcinoma) without clinical or pathologic characteristics of a well-defined treatable subset were eligible. All patients received paclitaxel, carboplatin, bevacizumab, and erlotinib. Treatment cycles were repeated at 21-day intervals. After four cycles, paclitaxel and carboplatin were discontinued; bevacizumab-erlotinib treatment was continued until tumor progression. Patients were initially evaluated for response after completion of two treatment cycles; re-evaluations occurred every 6 weeks thereafter.


RESULTS
Forty-nine of 60 patients (82%) completed four cycles of therapy, and 44 patients (73%) subsequently received maintenance bevacizumab and erlotinib. Thirty-two patients (53%) had major responses to treatment; an additional 18 patients had stable disease. After a median follow-up of 19 months, the median progression-free survival time was 8 months, with 38% of patients progression free at 1 year. The median survival time and 2-year overall survival rate were 12.6 months and 27%, respectively. Treatment was generally well tolerated, with a toxicity profile as predicted based on the known toxicities of each treatment component.


CONCLUSIONS
Empiric treatment with paclitaxel, carboplatin, bevacizumab, and erlotinib is effective and well tolerated as first-line treatment for patients with CUP. Further development of this regimen is warranted.
Hainsworth
John D
JD
Sarah Cannon Research Institute, 3322 West End Avenue, Suite 900, Nashville, Tennessee 37203, USA. jhainsworth@tnonc.com
Spigel
David R
DR
Thompson
Dana S
DS
Murphy
Patrick B
PB
Lane
Cassie M
CM
Waterhouse
David M
DM
Naot
Yuval
Y
Greco
F Anthony
FA
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D017239:Paclitaxel