Logistic regression model of fotemustine toxicity combining independent phase II studies.
BACKGROUND
To optimize fotemustine chemotherapy, the authors considered how to combine independent Phase II trials to predict the risk of first occurrence of severe toxicity as a function of initial patient characteristics.


METHODS
Clinical data from six Phase II trials were collected. Of the 478 patients enrolled 442 (male/female, 259/183; age range, 15-81 years) were evaluable for toxicity (1384 cycles of chemotherapy), including 221 with malignant malignant melanomas, 138 with primary brain tumors, 29 with lung carcinomas, 8 with head and neck carcinomas, and 46 with miscellaneous cancers. The influence of age, sex, performance status, type of tumor, number and location of metastases, and previous treatment by chemotherapy and/or radiotherapy was studied. The logistic regression method was applied to predict occurrence of leukopenia, thrombocytopenia, anemia, digestive tract, and/or hepatic toxicity.


RESULTS
Univariate analysis showed that predictive factors for hematologic toxicity were age (> 50 years), type of tumor (brain < melanoma < others), number of metastatic sites (> 3), location of metastases (nonvisceral), and previous chemotherapy. Performance status and previous radiotherapy did not affect the toxicity of fotemustine Nausea and vomiting were predictable based on the type of tumor (head and neck < lung < brain < melanoma < others), the number of metastatic sites (> three) and visceral metastases. Hepatic disorders occurred preferentially in patients with hepatic metastases and more than three metastatic sites. Individual risk of hematologic and hepatic toxicity for patients with melanoma and primary brain tumors was predicted using logistic regression models.


CONCLUSIONS
By combining clinical data from independent Phase II trials, the logistic model developed could predict the probability of fotemustine hematologic and hepatic toxicity.
Raymond
E
E
Service de Médecine Interne-Oncologie, Hôpital Saint-Antoine, Paris, France.
Haon
C
C
Boaziz
C
C
Coste
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000009:adverse effects*; D009943:Organophosphorus Compounds / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine