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Aims and Background: Salvage treatment of advanced colorectal cancer patients has not been well defined as yet, and new potentially active drugs or combinations should be evaluated for these situations., Methods: From February 1993 to September 1993, the combination of carboplatin (CBDCA) and etoposide (VP-16), both as 100 mg/m2 for three consecutive days, was administered to 17 colorectal cancer patients who had been previously subjected to FA-FU combination chemotherapy. The CBDCA + VP-16 treatment was repeated every 3 weeks. A total of 58 cycles was administered, and 16 patients were evaluable for response., Results: There was no objective response, but 2 stable diseases and 14 progressive diseases were observed. Toxicity was mild, with no WHO 3-4 grade toxicity., Conclusion: This combination chemotherapy was judged ineffective for pretreated colorectal cancer patients.

In rats repeatedly treated subcutaneously as infants with adriamycin in 2 cycles of 4 treatments each, the induction of ocular and dental abnormalities and tumors was studied. Cataracts appeared from 18 to 26 days in 80% of CD rats treated with 1.15 mg/kg/day of adriamycin and from 28 to 104 days in 55% of Wistar-Lewis rats given 0.75 mg/kg/day adriamycin. Abnormal growth of incisors was observed in 30% of the CD rats and in 44% of the Wistar-Lewis rats. At lower doses, no such abnormalities were found. At about 1 year after treatment, 100% of the CD rats treated with 0.75 mg/kg/day adriamycin and about 60% of the Wistar-Lewis rats treated with 0.75 and 0.5 mg/kg/day adriamycin developed tumors, which were histologically classified.

4-demethoxydaunorubicin was tested against experimental mouse leukemias, in comparison with doxirubicin and daunorubicin. 4-demethoxydaunorubicin, administered ip to mice bearing ascitic L1210 or P388 leukemia was 5 times more potent than daunorubicin and 10 times more potent than doxorubicin (potency established in relation to optimal antitumor doses). At the optimal doses, 4-demethoxydaunorubicin was as active as daunorubicin and less active than doxorubicin. 4-demethoxydaunorubicin, administered iv was 8 times more potent than daunorubicin and 4-5 times more potent than doxorubicin. At the optimal doses, 4-demethoxydaunorubicin was markedly more active than daunorubicin or doxorubicin in mice injected iv with 10(5) L1210 leukemia cells (early or late leukemia) or with 10(2) Gross leukemia cells. In mice given 2 X 10(6) Gross leukemia cells iv, 4-demethoxydaunorubicin was as active as doxorubicin when treatment was given iv on days 1, 5 and 9 for 4-demethoxydaunorubicin, and on days 1, 3 and 6 for daunorubicin and doxorubicin. 4-demethoxydaunorubicin administered orally was highly active against ascitic P388 leukemia and against L1210 and Gross leukemia inoculated iv.

Xeroradiography, a method of X-ray imaging based upon selenium photoconductivity, was used for the study of experimental osteosarcoma induced by MSV-M virus in rats. Due to the peculiar features of xeroradiographic image (enhancement of details and lowering of the overall contrast) good pictures of osseous structures together with soft tissues were obtained even in very young animals. Serially perfomred xeroradiographies gave a permanent representation of tumor evolution with time. Advantages and drawbacks of this method are discussed, particularly with respect to radiation dosage. Xeroradiography is proposed for the study of the response to antiblastic chemotherapy of experimental bone tumors.

Two cell lines derived from a primary MSV-M-induced tumor in a BALB/c mouse were studied. One line (MS-2) was subject only to continuous tissue culture transfer (tct). After 21 tct, MS-2 cells produced progressive tumors (MS-2 tumors) in syngeneic hosts. The second cell line (MS-2T) was established by cultivation of a MS-2 tumor. The ability to produce progressive tumors decreased with increased number of tct, in both cell lines. The virus content of MS-2 and MS-2T cells was very low, as shown by uridine incorporation and electron microscopy. Immmunofluorescence tests demonstrated that antigens different from the viral MSV-M antigens were present on the cell lines, and that antigenic changes occurred with increased number of tct. Serum of mice bearing progressive MS-2 tumors reacted with MS-2T cells when these cells produced progressive tumors and did not react with MS-2 cells when they produced regressing tumors. MS-2 cells producing regressing tumors reacted with serum from mice in which the MS-2 tumor had regressed and with serum from mice immunized with MS-2T cells at late tct when they were poorly oncogenic. The antigenic changes seemed, therefore, to parallel the decrease of malignancy. A chromosomal analysis carried out on MS-2 and MS-2T cells, when both produced progressive tumors, showed a modal number of 48 and 44, respectively. MS-2T cells showed a large acrocentric chromosome. In contrast, the MS-2 cells at late tct, when they gave regressing tumors, showed a modal number of 60 and a wide range of distribution of chromosome number.

The authors report a case of renal cell carcinoma metastasis to the pancreas occurring 25 years after nephrectomy. The need for prolonged follow-up of patients is emphasized. The surgical approach is considered the best way to deal with such late metastases.

This paper describes the effect of Tween 80 on the antitumor activity and on the distribution of adriamycin in mice. The dilution of adriamycin in a 10% water solution of Tween 80 produced a significant increase of the antitumor activity in mice against ascites tumors (L 1210 leukemia), disseminated leukemias (transplanted leukemias originally induced by Gross leukemai virus and Moloney leukemia virus), and solid tumors (Sarcoma 180, MS-2 sarcoma). In all these experiments the drug was administered i.v., according to different schedules. Higher antitumor activity at the optimal dose and an increase of activity at lower doses were observed in different experimental systems. Toxicity was also slightly enhanced. Tissue distribution was studied in normal mice and in tumor-bearing mice (Gross leukemia and MS-2 sarcoma). In animals give i.v. adriamycin diluted in 10% Tween 80 there was a higher drug concentration in spleen, lung and kidney than there was in mice given the drug in a water solution. In all the other organs examined (heart, liver, small intestine) and in the MS-2 tumor tissue, no significant increase was observed. In L1210 leukemia-bearing mice, i.p. treatment with adriamycin diluted in 10% Tween 80 resulted in a significantly higher toxicity than that which resulted from treatment with adriamycin in a wa ter solution; no increase of antitumor activity was observed.