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Cross-resistance to antineoplastic agents in a human small cell lung cancer subline resistant to okadaic acid
Abstracts /hg
Gmcer 13 (1995) 323-356
cells, topoisomerase IIa and 6 levels were increased approximately Zfold. Accordingly, the topoisomerase II-directed drug etoposide (VP16) induced an increased number of DNA single-strand breaks in NYH/ TPT cells. However, sensitivity to different topoisomerase II-targeting agents in m cells varied horn increased to decreased, indicating a role for as yet unidentified factors acting on the pathway to cell death after topoisomerase II-induced DNA damage has occurred. Of20 anticancer agents tested, only hydroxyurea showed marked collateral hypersensitivity in NYH/TPT cells.
OK-432 accelerates recovery from myelosuppression induced by combination chemotherapy for advanced lung cancer Kuroki S. Katoh 0. Yamada H. Respiratoy Dis. InternalMed. Dept., Socrol lnsurace Saga Hospital, l-6-38 TaJiise, Saga 840. Biotherapy (Japan) 1995;9:819-24. WC evaluated the efficacy of OK-432 for myelosuppression due to cancer chemotherapy, which consisted of CDDP, VP 16 and CBDCA. for advanced lung cancer patients. The treatments consisted of two courses. The first course was cancer chemotherapy alone and the second course a combination of chemotherapy and OK-432. The use of OK432 apparently alleviated the decrease in leukocyte. neutrophil and plalclct counts. Particularly, in the first case, both G-CSF and platelet transfusions. which were needed in the first course, were not necessary In the second course due to the combination with OK-432. These results mdlca(c that the combination of OK-432 may bc useful for alleviating myclosuppression due lo chemotherapy for lung cancer patients.
Cross-resistance to antineoplastic agents in a human small cell lung cancer subline resistant to okadaic acid Takeda Y, Kubota N, Nishio K, Funayama Y, Gemma A, Niitani H et al. Pharmacology Division, National Cancer Research Institute. 5-l-l Tsukij:. Chuo-ku, Tokyo 104. Oncol Rep 1995;2:705-10. We report on a human small cell lung cancer subline (H69/OAlOO) resistant to okadaic acid, an inhibitor of protein phosphatases. H69/ OAIOO showed cross-resistance to cisdiamminedichloroplatinum(I1) (CDDP), adriamycin, and vinca alkaloids, Intracellular retention of adriamycin and CDDP in H69/OAlOO was the same as those in H69. H69/OAlOO was not shown to express MDR-1 by the reverse transcription polymerasc chain reaction method. Expression level of mRNA of multidrug resistance-associated protein @lRP) in H69/OA 100 was the same as that in H69. These data suggest that the mechanism of drug resistance in H69/OAlOO might be due to a new mechanism of non-P-glycopmtein mediated multidrug resistance.
Evduation by using Fan Z-M, Clinical
of the treatment of 62 patients with advanced cancer lymphokincactivated killer cells plus interleukin-2 Zau B-R, Qiao C-H. Bethune-LavaI Oncology Unit, First College,
Norman
Bethune
Univ.
of Med.
Scis..
Changchun.
Chin J Clin Onwl 1995;22:502-6. Sixty-two patients with advanced cancer were treated with lymphokine-activated killer (LAK) cells derived from the fetal spleen along with interleukin-2 (IL-2). It was shown that this kind of LAK cells is as reliable and &ectlve as others. A partial response (PR) rate of 22.58% was achieved. As for cancer of kidney, melanoma, liver, lung, colon, thefigureawcm66.67%, 50.00%% 25.00%, 19.430/, 16.67% respectively. The median duration of PR was 15.95 months. The performance status before and during the treatment course of IL-Z/LAK cells were important tiers affecting the remission. The mortality was
345
20.97%. This immunotherapeutic approach can result in tumour regression, and good effect on metastatic lesion as well in some patients for whom no other effective therapy is available as yet. Further random trial is just&d. Chemotherapy with vincristinelifosfamidetcarboplatinf etoposide in small cell lung cancer brigan P, Sow Ming Lee, Be&her D, Woodhead M, Weir D, Hanky S et al. Department o/Medical Oncologv. Christie Hospital NHS Trust, Manchester A420 4BX. Semin Oncol 1995;22:Suppl 7:32-41. Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/ radiotherapy will be required to improve the survivaJ of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 26% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combinedmodality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens. Ifosfamiddcuboplatin/etoposide chemotherapy in patients with metastatic non-small cell lung cancer Chang AY, Asbury RF, Boros L, Garrow GC, Hsieh S. Department of Medicine, Universi& of Rochestee,: Genesee Hospital, 224 Alexander St, Rochester: NY 14607-4055. Semin Oncol 1995;22:Suppl 719-12.
We have evaluated the combination of ifosfamide, carboplatin, and etoposide (ICE) along with mesna in 46 patients with stage IV nonsmall cell lung cancer. Treatment consisted of ifosfamide (1.25 g/mYd with mesna) and etoposide (80 mg/mVd) given intravenously on days 1 to 3 and carboplatin (300 mg/m2) given intravenously on day 1 every 4 weeks, Eligibility criteria included measurable disease; adequate hematologic. hepatic, and renal functions; no prior chemotherapy; and an Eastern Cooperative Oncology Gmup performance status (PS) of 0 to 3. Two Patients were lost to follow-up and one had received prior chemotherapy, leaving 43 patients evaluable for response and toxicities. There were 27 male and 16 female patients. wenty- three patients had a PS of 0 or 1 and 20 had a PS of 2 or 3, Eighteen patients had received prior radiotherapy. There were two complete responses and nine partial responses. The response rate was 35% in PS 0 or I patients and 15% in PS 2 or 3 patients. The most frequent toxicity was myelosuppression: 44% of patients experienced grade 3 or 4 leukopenia and 14%. grade 3 or 4 thrombocytopenia. Patients receiving prior radiation were significantly more prone to develop leukopenia (P = .Ol). Five patients developed leukopenic fever, and three died of sepsis. Gastrointestinal toxicities were mostly mild. No neurologic or genitourinary toxicities were obserwd. The median length of survival was 209 days for patients with aPS of0 or I and 123 days for theentiregroup. The I-year survival rate was 22% and 19%. respectively, in these two patient subgroups. ICE is an active regimen in patients with metastatic non-small cell lung cancer and a good PS. Myelosuppression is the major dose-limiting toxicity, Hematopoietic growth factors may be indicated in subsequent: studies, especially in patients who had prior radiation therapy. The therapeutic effect of ICE on patients with a poor PS remains unsatisfactory and requires tkrther investigation.
Gmcer 13 (1995) 323-356
cells, topoisomerase IIa and 6 levels were increased approximately Zfold. Accordingly, the topoisomerase II-directed drug etoposide (VP16) induced an increased number of DNA single-strand breaks in NYH/ TPT cells. However, sensitivity to different topoisomerase II-targeting agents in m cells varied horn increased to decreased, indicating a role for as yet unidentified factors acting on the pathway to cell death after topoisomerase II-induced DNA damage has occurred. Of20 anticancer agents tested, only hydroxyurea showed marked collateral hypersensitivity in NYH/TPT cells.
OK-432 accelerates recovery from myelosuppression induced by combination chemotherapy for advanced lung cancer Kuroki S. Katoh 0. Yamada H. Respiratoy Dis. InternalMed. Dept., Socrol lnsurace Saga Hospital, l-6-38 TaJiise, Saga 840. Biotherapy (Japan) 1995;9:819-24. WC evaluated the efficacy of OK-432 for myelosuppression due to cancer chemotherapy, which consisted of CDDP, VP 16 and CBDCA. for advanced lung cancer patients. The treatments consisted of two courses. The first course was cancer chemotherapy alone and the second course a combination of chemotherapy and OK-432. The use of OK432 apparently alleviated the decrease in leukocyte. neutrophil and plalclct counts. Particularly, in the first case, both G-CSF and platelet transfusions. which were needed in the first course, were not necessary In the second course due to the combination with OK-432. These results mdlca(c that the combination of OK-432 may bc useful for alleviating myclosuppression due lo chemotherapy for lung cancer patients.
Cross-resistance to antineoplastic agents in a human small cell lung cancer subline resistant to okadaic acid Takeda Y, Kubota N, Nishio K, Funayama Y, Gemma A, Niitani H et al. Pharmacology Division, National Cancer Research Institute. 5-l-l Tsukij:. Chuo-ku, Tokyo 104. Oncol Rep 1995;2:705-10. We report on a human small cell lung cancer subline (H69/OAlOO) resistant to okadaic acid, an inhibitor of protein phosphatases. H69/ OAIOO showed cross-resistance to cisdiamminedichloroplatinum(I1) (CDDP), adriamycin, and vinca alkaloids, Intracellular retention of adriamycin and CDDP in H69/OAlOO was the same as those in H69. H69/OAlOO was not shown to express MDR-1 by the reverse transcription polymerasc chain reaction method. Expression level of mRNA of multidrug resistance-associated protein @lRP) in H69/OA 100 was the same as that in H69. These data suggest that the mechanism of drug resistance in H69/OAlOO might be due to a new mechanism of non-P-glycopmtein mediated multidrug resistance.
Evduation by using Fan Z-M, Clinical
of the treatment of 62 patients with advanced cancer lymphokincactivated killer cells plus interleukin-2 Zau B-R, Qiao C-H. Bethune-LavaI Oncology Unit, First College,
Norman
Bethune
Univ.
of Med.
Scis..
Changchun.
Chin J Clin Onwl 1995;22:502-6. Sixty-two patients with advanced cancer were treated with lymphokine-activated killer (LAK) cells derived from the fetal spleen along with interleukin-2 (IL-2). It was shown that this kind of LAK cells is as reliable and &ectlve as others. A partial response (PR) rate of 22.58% was achieved. As for cancer of kidney, melanoma, liver, lung, colon, thefigureawcm66.67%, 50.00%% 25.00%, 19.430/, 16.67% respectively. The median duration of PR was 15.95 months. The performance status before and during the treatment course of IL-Z/LAK cells were important tiers affecting the remission. The mortality was
345
20.97%. This immunotherapeutic approach can result in tumour regression, and good effect on metastatic lesion as well in some patients for whom no other effective therapy is available as yet. Further random trial is just&d. Chemotherapy with vincristinelifosfamidetcarboplatinf etoposide in small cell lung cancer brigan P, Sow Ming Lee, Be&her D, Woodhead M, Weir D, Hanky S et al. Department o/Medical Oncologv. Christie Hospital NHS Trust, Manchester A420 4BX. Semin Oncol 1995;22:Suppl 7:32-41. Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/ radiotherapy will be required to improve the survivaJ of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 26% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combinedmodality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens. Ifosfamiddcuboplatin/etoposide chemotherapy in patients with metastatic non-small cell lung cancer Chang AY, Asbury RF, Boros L, Garrow GC, Hsieh S. Department of Medicine, Universi& of Rochestee,: Genesee Hospital, 224 Alexander St, Rochester: NY 14607-4055. Semin Oncol 1995;22:Suppl 719-12.
We have evaluated the combination of ifosfamide, carboplatin, and etoposide (ICE) along with mesna in 46 patients with stage IV nonsmall cell lung cancer. Treatment consisted of ifosfamide (1.25 g/mYd with mesna) and etoposide (80 mg/mVd) given intravenously on days 1 to 3 and carboplatin (300 mg/m2) given intravenously on day 1 every 4 weeks, Eligibility criteria included measurable disease; adequate hematologic. hepatic, and renal functions; no prior chemotherapy; and an Eastern Cooperative Oncology Gmup performance status (PS) of 0 to 3. Two Patients were lost to follow-up and one had received prior chemotherapy, leaving 43 patients evaluable for response and toxicities. There were 27 male and 16 female patients. wenty- three patients had a PS of 0 or 1 and 20 had a PS of 2 or 3, Eighteen patients had received prior radiotherapy. There were two complete responses and nine partial responses. The response rate was 35% in PS 0 or I patients and 15% in PS 2 or 3 patients. The most frequent toxicity was myelosuppression: 44% of patients experienced grade 3 or 4 leukopenia and 14%. grade 3 or 4 thrombocytopenia. Patients receiving prior radiation were significantly more prone to develop leukopenia (P = .Ol). Five patients developed leukopenic fever, and three died of sepsis. Gastrointestinal toxicities were mostly mild. No neurologic or genitourinary toxicities were obserwd. The median length of survival was 209 days for patients with aPS of0 or I and 123 days for theentiregroup. The I-year survival rate was 22% and 19%. respectively, in these two patient subgroups. ICE is an active regimen in patients with metastatic non-small cell lung cancer and a good PS. Myelosuppression is the major dose-limiting toxicity, Hematopoietic growth factors may be indicated in subsequent: studies, especially in patients who had prior radiation therapy. The therapeutic effect of ICE on patients with a poor PS remains unsatisfactory and requires tkrther investigation.