Anti-cancer drugs
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The benzyl-substituted unbridged titanocene bis-[(p-methoxybenzyl)cyclopentadienyl] titanium(IV) dichloride (Titanocene Y) was tested in vitro against human renal cancer cells (Caki-1), in which it showed an IC50 value of 36 x 10 mol/l. Titanocene Y was then given in vivo in doses of 10, 20, 30, 40 and 50 mg/kg on 5 consecutive days to Caki-1-bearing mice, and it showed concentration-dependent and statistically significant tumor growth reduction with respect to a solvent-treated control cohort. The maximum tolerable dose of Titanocene Y was determined to be 40 mg/kg and it showed significantly better tumor volume growth reduction than cisplatin given at a dose of 2 mg/kg. This superior activity of Titanocene Y with respect to cisplatin will hopefully lead to clinical tests against metastatic renal cell cancer in the near future.
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The aim of the present study was to examine modifications of anti-tumor activity and toxicity of paclitaxel (PLX) when given p.o. after recombinant interleukin-2 (rIL-2) to Lewis lung carcinoma-bearing mice. PLX was given orally to mice at the dose of 15 mg/kg on day 8 and 30 mg/kg on day 15, either alone or after 16.5 microg of rIL-2 given i.p. twice a day either 1 or 3 days before. ⋯ Lung metastasis was significantly lower and s.c. tumors were smaller in the PLX+rIL-2 group than in the PLX or rIL-2 or non-treated groups. In addition, a decrease in lung P-glycoprotein expression (investigated by Western blot analysis) was observed 1 h after the last administration of rIL-2 on day 7.
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Radiation recall refers to inflammatory reactions triggered by chemotherapeutic agents and develops cutaneously in the previously irradiated areas. Such agents include anthracyclines, taxanes and capecitabine. Radiation recall related to gemcitabine has been reported in lung and breast cancer. ⋯ Treating physicians must be aware of this potential toxicity from gemcitabine either given concomitantly or followed by radiation. We suggest discontinuing gemcitabine if radiation recall is observed. Further studies are warranted into the pathogenesis of this unique phenomenon.
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The aim of this work was 2-fold: (i) to identify correlations between the activities of pairs of 19 anti-tumor agents in a mini-panel of 14 human cancer cell lines of diverse origins with the goal of validating the panel, and (ii) to look for correlations between the activities of 19 standard anti-tumor agents and the intracellular concentrations of glutathione (GSH). Validation with analogous data from the National Cancer Institute (NCI) Developmental Therapeutics Program was made. The cell growth inhibition potencies of the anti-tumor agents [cisplatin, carboplatin, oxaliplatin, DACH-Pt, melphalan, chlorambucil, thiotepa, busulfan, doxorubicin, etoposide, camptothecin, vinblastine, podophyllotoxin, colchicine, taxol, hydroxyurea, methotrexate, 5-azacytidine and 5-fluorouracil (5-FU)] were estimated in 14 cancer cell lines by their GI50 values. ⋯ In conclusion, a panel of 14 human cancer cell lines of diverse origin was used to identify similarities and differences in the activities of standard anti-tumor agents. The level of significance was stronger with the 34 cell lines of the NCI, however. Our results indicate that GSH intracellular concentrations correlate with resistance only with doxorubicin and thiotepa in these cell lines.
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Case Reports
Delayed oxaliplatin-associated neurotoxicity following adjuvant chemotherapy for stage III colon cancer.
Oxaliplatin-containing chemotherapy regimens are utilized commonly for metastatic colorectal cancer and increasingly in the adjuvant setting following surgical resection. The dose-limiting toxicity is neurotoxicity. Acute neurotoxicity is cold induced and transient. ⋯ We report here a case of a patient who developed significant grade 3 chronic neuropathy following completion of 6 months of adjuvant oxaliplatin-containing chemotherapy for stage III colon cancer. The neurotoxicity was not preceded by any transient symptoms characteristic of chronic oxaliplatin neuropathy and its onset was unpredictable. Delayed neurotoxicity is a complication which must be considered for patients receiving adjuvant therapy and attempts to utilize the minimum effective cumulative dose of oxaliplatin are warranted.