Radioimmunotherapy of small cell lung carcinoma with the two-step method using a bispecific anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid (DTPA) antibody and iodine-131 Di-DTPA hapten: results of a phase I/II trial.
As small cell lung carcinoma (SCLC) is frequently a widespread disease at diagnosis, highly radiosensitive and often only partially responsive to chemotherapy, radioimmunotherapy (RIT) would appear to be a promising technique for treatment. We report the preliminary results of a Phase I/II trial of RIT in SCLC using a two-step method and a myeloablative protocol with circulating stem cells transplantation. Fourteen patients with proved SCLC relapse after chemotherapy were treated with RIT. They were first injected i.v. with a bispecific (anti-carcinoembryonic antigen/anti-diethylenetriaminepentaacetic acid) monoclonal antibody (20-80 mg in 100 ml of saline solution) and then 4 days later with di-(In-diethylenetriaminepentaacetic acid)-tyrosyl-lysine hapten labeled with 1.48-6.66 GBq (40-180 mCi) of I-131 and diluted in 100 ml of saline solution. In patients receiving 150 mCi or more, circulating stem cells were harvested before treatment and reinfused 10-15 days later. Treatment response was evaluated by CT and biochemical data during the month before and 1, 3, 6, and 12 months after treatment. All patients received the scheduled dose without immediate adverse reactions to bispecific antibody or 1-131 hapten. Toxicity was mainly hematological, with two cases of grade 2 leukopenia and three cases of grade 3 or 4 thrombopenia. Body scanning 8 days after injection of the radiolabeled hapten generally showed good uptake at the tumor sites. Estimated tumor dose was 2.6-32.2 cGy/mCi. Among the 12 patients evaluated to date, we have observed 9 progressions, 2 partial responses (one almost complete for 3 months), and 1 stabilization of more than 24 months. Efficiency and toxicity were dose-related. The maximal tolerable dose without hematological rescue was 150 mCi. These preliminary results are encouraging, and dose escalation is currently continuing to reach 300 mCi. RIT should prove to be an interesting therapeutic method for SCLC, although repeated injections and hematological rescue will probably be required, as well as combination with other treatment modalities.
Vuillez
J P
JP
Nuclear Medicine Department, University Hospital, Grenoble, France.
Kraeber-Bodéré
F
F
Moro
D
D
Bardiès
M
M
Douillard
J Y
JY
Gautherot
E
E
Rouvier
E
E
Barbet
J
J
Garban
F
F
Moreau
P
P
Chatal
J F
JF
D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D018288:Carcinoma, Small Cell / Q000532:radiotherapy*; D005260:Female; D006241:Haptens / Q000627:therapeutic use*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D004369:Pentetic Acid / Q000276:immunology*; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage
D000888:Antibodies, Anti-Idiotypic; D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; D006241:Haptens; D007457:Iodine Radioisotopes; D004369:Pentetic Acid