[Use of etoposide, ifosfamide and cisplatin (EIP) for treatment of inoperable non-small cell lung cancer]. / Zastosowanie Etopozydu, ifosfamidu i Cysplatyny (EIP) w leczeniu nieoperacyjnych postaci niedrobnokomórkowego raka pluca.

Recent studies have pointed out that chemotherapy can prolong life in advanced inoperable cancer patients. A clinical study to evaluate response and toxicity of the combination of etoposide, ifosfamide and cisplatin (EIP) in the treatment of inoperable non-small cell lung cancer was performed. 25 patients entered the study. Treatment consisted of etoposide 120 mg/m2 given i.v. on days 1-3, ifosfamide 1.5 g/m2 given i.v. on days 1-5 with mesna protection and cisplatin 20 mg/m2 given i.v. on days 1-5. Cycles were repeated every 4 weeks for a maximum of 6 in responders. 16 (64%) patients responded to treatment, 13 (52%) reached partial and 3 (12%) complete remission. In two recurrent cases second remission was achieved after reinstitution of the EIP regimen. Median survival time was 13 months (range 7-48 months) for responders and 5 months (range 2-11 months) for non-responders. Overall treatment was well tolerated with granulocytopenia being the most frequent toxicity. The results are encouraging for further investigations. Application of higher doses of ifosfamide with colony stimulating factors protection is planned.

[Prognostic factors and results of treating 42 patients with nln-seminomatous germ cell tumor of the testis]. / Czynniki prognostyczne i wyniki leczenia 42 chorych z nienasieniakowymi guzami jader.

In 1984-1988, 42 patients with non-seminomatous germ-cell tumour of the testis were treated surgically in combination with chemotherapy. Actually, 21 (50%) patients live without any symptoms, 5 (12%) patients with the symptoms during treatment whereas 6 (38%) patients died. Survival period of cured patients was 10-50 months (median 29 months) while still treated patients--5-34 months (median 10 months). A relationship between clinical outcome and advancement and tumor weight was noted. A decrease in the velocity of tumor weight increase with time lapse was seen. Inherited defects of the uro-genital tract were diagnosed in 6 (14%) patients.

[Comparison of the cytotoxic activity of doxorubicin and epirubicin by an in vitro test]. / Porównanie aktywnosci cytotoksycznej doksorubicyny i epirubicyny testem in vitro.

In a group of 34 tumours representing 9 various human neoplasms the cytotoxic activity was compared of doxorubicin (Adriamycin) and epirubicin (Farmorubicin) in vitro. The method was based on measurements of the degree of inhibition of 3H-uridine incorporation in a suspension of cells of the tumour incubated with the cytostatic agent as compared to the activity in the control group. In 7 cases (21%) the tumours were sensitive to both agents, 26 tumours (76%) failed to respond to either drug. In one case the tumour responded only to epirubicin (3%) which suggests a probable incomplete cross-resistance between both cytostatics. A positive correlation between increased concentration of the drugs used in this experiment and the increase of the cytostatic effect in the group of tumours sensitive in vitro suggests the necessity of raising the dosage of less toxic epirubicin in clinical trials.

Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine.

The stereospecific synthesis of two chiral metabolites of ifosfamide (2), 4-ketoifosfamide (5) and 2-amino-3-(2-chloroethyl)tetrahydro-2H-1,3, 2-oxazaphosphorine 2-oxide (9), is reported. The absolute configuration of both compounds was assigned on the basis of chemical correlation. In addition, two other achiral metabolites of 2, carboxyifosfamide (6) and IPAM (7), were synthesized. These and other organophosphorus metabolites of ifosfamide were found, by 31P NMR, in the urine of patients to whom racemic 2 was administered. The measurements performed in the presence of optically active lanthanide shift reagent [Eu(tfc)3] showed considerable stereoselectivity of in vivo formation of some chiral metabolites of ifosfamide.