Carcinoma of unknown primary site: sequential treatment with paclitaxel/carboplatin/etoposide and gemcitabine/irinotecan: a Minnie Pearl Cancer Research Network phase II trial.
OBJECTIVE
To evaluate the efficacy and toxicity of the sequential administration of paclitaxel (Taxol; Bristol-Myers Squibb; Princeton, NJ), carboplatin (Paraplatin; Bristol-Myers Squibb), and oral etoposide (VePesid; Bristol-Myers Squibb) followed by gemcitabine (Gemzar; Eli Lilly; Indianapolis, IN) and irinotecan (Campostar; Pfizer Pharmaceuticals; New York, NY) in the first-line treatment of patients with carcinoma of unknown primary site.


METHODS
One hundred thirty-two patients were treated with sequential combination chemotherapy for a maximum of six cycles. All patients had relatively poor prognostic features. Fifty-nine patients had well-differentiated adenocarcinoma, 73 patients had poorly differentiated carcinoma, and 121 patients had performance status scores of 0 or 1.


RESULTS
Thirty-three (30%) of 111 assessable patients (95% confidence interval 27%-33%) had objective responses to treatment (26 partial responses, seven complete responses). The combination of gemcitabine and irinotecan was associated with significantly less toxicity than the triple-drug regimen and improved the responses in several patients (10%). The response rates were similar in the two major histologic tumor types, but were lower for patients with liver-dominant tumors (13%) and higher for patients with lymph-node-dominant tumors (50%). The median progression-free survival time, median survival time, and actuarial survival rates at 1 and 2 years were 5.7 months, 9.1 months, 35%, and 16%, respectively.


CONCLUSIONS
Sequential combination chemotherapy with paclitaxel/carboplatin/oral etoposide and gemcitabine/irinotecan is an active treatment for patients with carcinoma of unknown primary site, but overall toxicities are greater than those seen with other combinations of new drugs and survival appears similar to that observed in 264 other patients treated in our four previous phase II trials. A better understanding of the biology of these heterogeneous tumors will likely lead to improved therapy for these patients.
Greco
F Anthony
FA
Sarah Cannon Cancer Center, 250 25th Avenue North, Suite 110, Nashville, Tennessee 37203, USA. fgreco@tnonc.com
Rodriguez
Gladys I
GI
Shaffer
Don W
DW
Hermann
Robert
R
Litchy
Sharlene
S
Yardley
Denise A
DA
Burris
Howard A
HA
Morrissey
Lisa H
LH
Erland
Joan B
JB
Hainsworth
John D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D005047:Etoposide; D000077146:Irinotecan; D016190:Carboplatin; D017239:Paclitaxel; D002166:Camptothecin; D000093542:Gemcitabine