The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I...
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Abstracts/Lung Gmcer 14 (19%) 377-408 401 and carcinoicls. RT-PCR-showed that the MRP-positiveadenocarc inomas and squamous-cell carcinomas expressed mrp mRNA significantly. lmmunoelectron microscopically) MRP was localixed in the plasma membraneand rough endoplasmic reticulum, It is thus important to take MRP into account when considering chemotherapy for lung cancers because levels of mdr 1 gene product, another multidrug-resistance gene family, are low in untreated lung cancers. Cytostatic chemotherapy for small cell lung cancer in patients of age 75 years or older Berxinec P, Ktoslak M, P&&k S, Arpasova M, KuxmovaH. Department of Oncology, Inst. of TE and Respiratory Diseases. Puskinova 134, 949.88 Nitra. Radio1 Oncol 1995;29:236-9. Eleven patients of age 75 years or older with histologically and/or cytologically proven small cell lung cancer [SCLC) were treated at our institution during the period of 5 years 1990-1994. Patients characteristics: IOmen, 1 woman, age: median: 77, range: 75-82years, performance status WHO ?4 3. Treatment: different treatment schedules were used according to patients status and comorbidity. Single drug therapy with teniposide or etoposide was used in five patients, in six patients further cytostatics (mostly carboplatin) were used in addition. Results: response rate after 2 cowses of therapy: complete response: 1 (9 W), partial response: 5 (45 %), stable disease: 3 (27 W), progression: 2 (18%). survival time: median: 7.5, range: l-32 + months, adverse effects: except for 3 leukopenias (2x WHO grade 3, lx WHO grade 4) no serious adverse effects. Conclusion: currently available cytostatics for SCLC, especially epipodophyllotoxins aloneor in combination with carboplatin, seem to beeffectiveand (with adequatepremedication) well tolerated even in very old patients. The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I trial Albrecht CF, Kruger PB, Smit BJ, Freestone M, Gouws L, Miller Ret al. DepanmentofPharmacol, UniversiryofStellenbosdr, Tygerberg, W Cape. S Afr Med J 1995;85:861-5. Objecrive. To study the pharmacokinetic behaviour of hypoxoside taken orally by 24 patients with lung cancer. Design. Random&d open study with three single doses of I 600,2 400 and 3 ZOO mg standardised Hypoxis plant extract (200 mg capsules) and a multiple-dose. study on the first 6 patients taking 4 capsules 3 times daily for 11 days. Participants and setting. Patients with histologically proven squamous, large-cell oradenocarcinoma werehospitalised at the Radiation Oncology Ward, Karl Bremer Hospital, Bellville. W Cape. Methods. Blood was drawn at regular intervals up to 75 hours after single doses and the concentrations of metabolites of the aglucone of hypoxoside, rooperol, were measured with a high-performance liquid chromatography method. For the multipledose study blood was drawn before the first dose each day. Concentration-time relationships were analysed according to a conventional single open-compartment model and also by using the NONMEM digital computer programme. Results. Neither hypoxoside nor rooperol appear in circulation. This is due to complete phase II biotransformation to diglucuronide, disulphate and mixed glucuronide- sulphate metabolites, of which the latter is the major component. Considerable interpatient variation in concentration-time relationships was found in the singledose studies. It was due to an active entetohepatic recirculation in some patients and a distinct lag phase in others together with zero-order rate of formation of rooperol in the colon. Computer modelling indicated a single open-compartment model in which the mass of the patient did not influence volume of distribution and clearance because formation of the metabolites is dependent on the metabolising capacity of the patient. However, the elimination of the metabolites follows first-order kinetics with half-lives ranging from 50 hours for the major metabolite to 20 hours for the two minor metabolites. Multiple-dose studies also showed large interpatient variation. Conclusion. In order to reach metabolite levels near 100 g/ml, which have been shown to be tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to be individualised for each patient. For most patients, however, a daily dose of 2 400 mg was sufficient. Tumour response evaluation during lung cancer chemotherapy Pujol JL, Parrat E, Ray P, Lehmann hi, Gautier V, Michel FB. Service des Maladies Respiratoires. CHU, HopitalAmaud-de-Villeneuve, 555, Route de Ganges, 34295 Montpellier Ceder. Rev Med lnterne 1995;16:759-66. Chemotherapy of lung cancer is still an experimental approach requiring careful evaluation. Tumour response (marker of anticancer activity) is not perfectly correlated to survival (marker of chemotherapy efficacy), but its evaluation remains a milestone in as much as reporting a wrong tumour response rate might lead to the rejection of active new treatments. This review deals with the method of tumour response measurements and its use during a chemotherapy protocol. Recommendations drawn from the analysis of the literature are: 1) to assess and classify all lesions which can be identified at the beginning of the treatment; 2) to define the target lesions, mainly the ones which can bebidimensionally measured; 3) to use the World Health Organization recommendations for reporting the overall response; 4) to confirm complete response by negative rebiopsies; 5) to avoid second fiberoptic bronchoscopy to patients with stableor progressive disease on CT-scan, and finally; 6) toassess response quality by evaluating responseduration and improvement of quality of life. Interleukin-la and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: Comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF Gamier V, Pujol J-L, Michel F-B. CHR HopitalArnattdde Villeneuve, Service de Maladies Respiratoires, Av. Doyen G Giraud, 34295 Montpellier. Lung Cancer (Ireland) 1995; 13: 145-53. This study was designed to analyze the possible immunomodulation induced in viva by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-l, IL-6, TNFa and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-la decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF. Evaluation of rGCSF subcutaneous administration in two separate doses in chemotherapy for primary lung cancer patients Hiramori N, Hashimoto S, Kasamatsu Y, Hats H. Department of Internal Medicine, Kyoto Second Red Cross Hospital, 355-5 Haruobi rho, Marutamachi agaru, Kamigyo-ku, Kyoto 602. Biotherapy (Japan) 1995;9: 1195-g.
Transcript of The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I...
Abstracts/Lung Gmcer 14 (19%) 377-408 401
and carcinoicls. RT-PCR-showed that the MRP-positiveadenocarc inomas and squamous-cell carcinomas expressed mrp mRNA significantly. lmmunoelectron microscopically) MRP was localixed in the plasma membraneand rough endoplasmic reticulum, It is thus important to take MRP into account when considering chemotherapy for lung cancers because levels of mdr 1 gene product, another multidrug-resistance gene family, are low in untreated lung cancers.
Cytostatic chemotherapy for small cell lung cancer in patients of age 75 years or older Berxinec P, Ktoslak M, P&&k S, Arpasova M, KuxmovaH. Department of Oncology, Inst. of TE and Respiratory Diseases. Puskinova 134, 949.88 Nitra. Radio1 Oncol 1995;29:236-9.
Eleven patients of age 75 years or older with histologically and/or cytologically proven small cell lung cancer [SCLC) were treated at our institution during the period of 5 years 1990-1994. Patients characteristics: IOmen, 1 woman, age: median: 77, range: 75-82years, performance status WHO ?4 3. Treatment: different treatment schedules were used according to patients status and comorbidity. Single drug therapy with teniposide or etoposide was used in five patients, in six patients further cytostatics (mostly carboplatin) were used in addition. Results: response rate after 2 cowses of therapy: complete response: 1 (9 W), partial response: 5 (45 %), stable disease: 3 (27 W), progression: 2 (18%). survival time: median: 7.5, range: l-32 + months, adverse effects: except for 3 leukopenias (2x WHO grade 3, lx WHO grade 4) no serious adverse effects. Conclusion: currently available cytostatics for SCLC, especially epipodophyllotoxins aloneor in combination with carboplatin, seem to beeffectiveand (with adequatepremedication) well tolerated even in very old patients.
The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I trial Albrecht CF, Kruger PB, Smit BJ, Freestone M, Gouws L, Miller Ret al. DepanmentofPharmacol, UniversiryofStellenbosdr, Tygerberg, W Cape. S Afr Med J 1995;85:861-5.
Objecrive. To study the pharmacokinetic behaviour of hypoxoside taken orally by 24 patients with lung cancer. Design. Random&d open study with three single doses of I 600,2 400 and 3 ZOO mg standardised Hypoxis plant extract (200 mg capsules) and a multiple-dose. study on the first 6 patients taking 4 capsules 3 times daily for 11 days. Participants and setting. Patients with histologically proven squamous, large-cell oradenocarcinoma werehospitalised at the Radiation Oncology Ward, Karl Bremer Hospital, Bellville. W Cape. Methods. Blood was drawn at regular intervals up to 75 hours after single doses and the concentrations of metabolites of the aglucone of hypoxoside, rooperol, were measured with a high-performance liquid chromatography method. For the multipledose study blood was drawn before the first dose each day. Concentration-time relationships were analysed according to a conventional single open-compartment model and also by using the NONMEM digital computer programme. Results. Neither hypoxoside nor rooperol appear in circulation. This is due to complete phase II biotransformation to diglucuronide, disulphate and mixed glucuronide- sulphate metabolites, of which the latter is the major component. Considerable interpatient variation in concentration-time relationships was found in the singledose studies. It was due to an active entetohepatic recirculation in some patients and a distinct lag phase in others together with zero-order rate of formation of rooperol in the colon. Computer modelling indicated a single open-compartment model in which the mass of the patient did not influence volume of distribution and clearance because formation of the metabolites is dependent on the metabolising capacity of the patient. However, the elimination of the metabolites follows first-order kinetics with half-lives ranging from 50 hours for the major metabolite to 20 hours for the two minor metabolites.
Multiple-dose studies also showed large interpatient variation. Conclusion. In order to reach metabolite levels near 100 g/ml, which have been shown to be tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to be individualised for each patient. For most patients, however, a daily dose of 2 400 mg was sufficient.
Tumour response evaluation during lung cancer chemotherapy Pujol JL, Parrat E, Ray P, Lehmann hi, Gautier V, Michel FB. Service des Maladies Respiratoires. CHU, HopitalAmaud-de-Villeneuve, 555, Route de Ganges, 34295 Montpellier Ceder. Rev Med lnterne 1995;16:759-66.
Chemotherapy of lung cancer is still an experimental approach requiring careful evaluation. Tumour response (marker of anticancer activity) is not perfectly correlated to survival (marker of chemotherapy efficacy), but its evaluation remains a milestone in as much as reporting a wrong tumour response rate might lead to the rejection of active new treatments. This review deals with the method of tumour response measurements and its use during a chemotherapy protocol. Recommendations drawn from the analysis of the literature are: 1) to assess and classify all lesions which can be identified at the beginning of the treatment; 2) to define the target lesions, mainly the ones which can bebidimensionally measured; 3) to use the World Health Organization recommendations for reporting the overall response; 4) to confirm complete response by negative rebiopsies; 5) to avoid second fiberoptic bronchoscopy to patients with stableor progressive disease on CT-scan, and finally; 6) toassess response quality by evaluating responseduration and improvement of quality of life.
Interleukin-la and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: Comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF Gamier V, Pujol J-L, Michel F-B. CHR HopitalArnattdde Villeneuve, Service de Maladies Respiratoires, Av. Doyen G Giraud, 34295 Montpellier. Lung Cancer (Ireland) 1995; 13: 145-53.
This study was designed to analyze the possible immunomodulation induced in viva by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-l, IL-6, TNFa and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-la decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.
Evaluation of rGCSF subcutaneous administration in two separate doses in chemotherapy for primary lung cancer patients Hiramori N, Hashimoto S, Kasamatsu Y, Hats H. Department of Internal Medicine, Kyoto Second Red Cross Hospital, 355-5 Haruobi rho, Marutamachi agaru, Kamigyo-ku, Kyoto 602. Biotherapy (Japan) 1995;9: 1195-g.
