Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer.
An epidermal growth factor (EGF) vaccine was given before and after standard first line chemotherapy to patients with advanced nonsmall cell lung cancer (NSCLC), to investigate the immunologic and clinical results in a phase 1 study. Twenty patients diagnosed with advanced NSCLC were recruited. Two vaccinations were given before the first line of chemotherapy treatment, with subsequent monthly vaccination after concluding chemotherapy. The EGF vaccination dose was increased compared with previous trials; the primary end points were immunogenicity and safety. Anti-EGF antibody titers were more than 20 times higher than those previously obtained, without any increase in adverse events, serum EGF concentration decreased to undetectable levels in all patients. Ninety-two percent of the evaluated patients (n=13) showed an immunodominant antibody response against the central region on the EGF molecule. High percentages of EGF/EGF receptor binding inhibition were observed, which significantly positively correlated with the increased antibody response against the EGF immunodominant region. Survival of the patients in this study correlates positively with antibody titers. This study has shown that combination of EGF vaccination at high dose, with chemotherapy is feasible and well tolerated higher anti-EGF antibody titers and reduction of serum EGF concentration seen; do not entail an increase in severe adverse events. The correlation of survival with antibody titers observed is being confirmed confirmation in a wider and randomized trial currently ongoing.
Neninger
Elia
E
Hermanos Ameijeiras Hospital, Centro Habana, Havana, Cuba.
Verdecia
Beatriz García
BG
Crombet
Tania
T
Viada
Carmen
C
Pereda
Susana
S
Leonard
Idrissa
I
Mazorra
Zaima
Z
Fleites
Gladys
G
González
Marta
M
Wilkinson
Bárbara
B
González
Gisela
G
Lage
Agustín
A
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
D000906:Antibodies; D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D003520:Cyclophosphamide; C512478:EGFR protein, human; D066246:ErbB Receptors