[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study].
OBJECTIVE
Therapies involving a radical operation and radiation treatment for cervical carcinoma in stages I and II are not sufficiently effective in patient subgroups with high risk for recurrence. In recent publications, patients with high risk cervical cancer had with adjuvant simultaneous radio-chemotherapy a better disease free and overall survival but a higher toxicity compared with patients received an adjuvant radiotherapy alone.


METHODS
34 patients with at least 2 risk factors for recurrence of cervical cancer were treated with adjuvant chemotherapy after radical hysterectomy. The protocol consisted of 3 cycles of ifosfamide 1.6 g/m2 (d 1-3) and carboplatin (AUC 4, d1) every three weeks. For cell protection 21 patients received amifostine 740 mg/m2 d1-3; this was followed by standard radiation therapy (50.4 Gy percutaneous and high-dose-rate-after-loading for 21 patients, 2 x 5 Gy). The dose determination of the substances and their toxicity were investigated.


RESULTS
Patient (p) data: Median age 43 years (range: 25-70); pT1b-2a: n = 22; pT2b: n = 12; pN1: n = 28; pN0: n = 6; G3: n = 10; adeno- and adenosquamous carcinoma: n = 9, G3: n = 10, R1-resection: n = 5. 70.6% of these high-risk patients were disease-free after a median observation time of 40 (18-62) months. Median number of cycles of chemotherapy: 2.8. There was no more dose escalation than carboplatin according to AUC 4 possible. Hematologic toxicity (CTC grading, % of 96 documented cycles): anemia-grade 3-4: 30; -grade 1-2: 10.4; leukopenia-grade 3-4: 13, -grade 1-2: 21.7; alopecia-grade 3: all p.; cerebral neurotoxicity-grade 3-4: 8.3, -grade 1-2; 17.7; diarrhea under radiotherapy-grade 3-4: 2 p., -grade 1-2: 6 p.


CONCLUSIONS
This combined sequential adjuvant therapy was effective and had an acceptable level of toxicity. A phase III study comparing adjuvant sequential chemo-radiotherapy with and without Erythropoeitin to counteract the negative effects of anemia started in Germany in 1999 and had randomized now about 270 patients.
Blohmer
J U
JU
Klinik für Geburtshilfe und Frauenheilkunde der Charité, Humboldt-Universität zu Berlin. jens-u.blohmer@charite.de
Paepke
S
S
Böhmer
D
D
Ernhardt
B
B
Sehouli
J
J
Elling
D
D
Lichtenegger
W
W
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007044:Hysterectomy; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery
D016190:Carboplatin; D004999:Amifostine; D007069:Ifosfamide