1
s34 from untreated small cell lung cancer patients were the most chemosen- sitive for adriamycin, melphalan, vincristine and VP16 compared to the other cell types. In addition, untreated SCLC was more sensitive than non-SCLC to BCNU and cis-platin, while vincristine was the only drug to which treated SCLC was more sensitive compared to the non-SCLC lines. In contrast, no significant differences between the lung cancer types wereobserved for vinblastine. Thus, this panel of lung cancer cells exhibited a drug sensitivity profile paralleling that observed in clinical practice. These results suggest that this lung cancer cell line panel in combination with a relatively simple but reproducible chemosensitivity assay, such as the M’lT assay, has potential for the testing of drug combinations and evaluating new anti-cancer agents in vitro. Cisplatin, adriamicin and etoposid in lung oat cell cancer. De La Torre MA, Borau MJ, Gonzalez E, Nieto J, Lopez-Lam F. Servicio de Radioterapia y Oncologia de1 Hospital Clinic0 Universi- tario de Valladolid, 47005 Valladolid. Oncologia 1988;11:181-6. Have been evaluated 23 patients with oat cell carcinoma of the lung afterthreecoursesofchemotherapyinCAVregimen(CDDP60mg/m*, ADM50mg/m2andVP-16120mg/m2x3),fromjanuary’85tofebruary ‘87. After this therapy the limited disease (EL) patients with remission (partial or complete) received consolidated radiotherapy and again chemotherapy until1 ADM tolerance dosis. The extended disease (EE) patients received the same regimen of chemotherapy and radiotherapy only was indicated with paliative and individualiced character. The completeresponse(CR)ratewas60% inELpatientsand431inEE.The partial remission (PR) rate was 30% in cases with EL and 14% in cases with BE. The CR patients has more increasing survival than PRpatients. The toxicity consisted essentially in myelosuppression (Grade I-II of WHO graduation), nausea-vomiting (Grade I-II) and alopecia (Grade III). Evaluation of fludarabine phosphate in small cell carcinoma. A Southwest Oncology Group study. Rainey JM, Hill JB, Crowley J. Louisiana Slate Universiry Medical Center, Lufayette, LA. Invest New Drugs. 1988;6:45-6. Fludarabine phosphate was given as a 5 day bolus infection to eleven evaluablepgtientswithrecurrentsmallcelIlungcarcinoma.Patientshad failed on one prior treatment regimen. There were no responses in the eleven evaluable patients. Severe neurofogic toxicity occurred in one patient. Fhidarabine phosphate as given in this protocol was not an effective agent in recurrent small cell lung carcinoma. Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer. Mattson K, Maasilta P, Tammilehto L, Holsti LR, Grove W. Department of Pulmonary Medicine, Helsinki University Cennal HOS- pital, Helsinki 29. Semin Oncol 1988;15(Suppl2):32-7. To determine the maximum tolerated dose (MTD) of uimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrex- ate in dosages ranging from 3 to 13.5 mg/m*/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m”,on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%). leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity in- cluded nausea and vomiting (67%), mucositis (30%). and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cycle- phosphamide was 7.5 mg/m*/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m?day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%). I2 patientsachievedstabledisease(54%),andfivepatientshadprogressive disease. Results suggest that trimetrexate 10.5 mg/m?day in combina- tion with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing. Clinical response to trimetrexate as sole therapy for nonsmall cell lung cancer. Maroun J. Ontario Cancer Foundation, Ouawa Clinic, General Divi- sion, Orrawa, Onr. KZH 8L6. Semin Oncol 1988;15(Suppl2):17-21. Trimetrexate glucuronate was evaluated in 70 nonsmall cell lung cancer patients with incurable disease and/or demonstrated progression following surgery/radiotherapy and no prior cytotoxic chemotherapy. Trimetrexate was initially administered at 8 mg/m* intravenously (IV) daily for 5 days and repeated every 3 to 4 weeks with dose adjustments depending on patient tolerance. A median of two courses oftrimetrexate therapy wasadministered(range 1 to 12).Fifty_nine(84%)patientswere evaluable for reswnse. Eleven uatients (19%) achieved a partial re- Trimetrexate combined with cisplatin or etoposide in the treatment of nonsmall cell lung cancer: A pilot study. Maroun JA, Natale RB, Robert F. Oftawa General Hospiral. Ottawa, On?. Semin Oncol 1988;15(Suppl2):38-40. Trimetrexate glucuronate in combination therapy with cisplatin or etowside was evaluated in nonsmall cell lunz cancer patients in a pilot, dose escalation study. Trimetrexate was administered intravenously together with 20 mg/m’cisplatin or 50 mg/m” etoposide for 5 consecu- tive days at an initial dose of 4 mg/m’. Courses were repeated at 3 week intervals with the trimetrexate dosage escalated according to patient tolerance. In the 12 patients treated to date, reversible myelosuppres- sion, consisting of leukopenia and thrombocytopenia, and nonhematol- ogic grade 1 and 2 toxicities were observed. The study is ongoing. The maximum tolerated trimetrexate dosage levels in combination therapy will be established. . sponse with a median duration of 15.3 weeks. The median time to response was4.6 weeks. Twenty-three patients (39%) had stable disease with a median time to progression of 15.7 weeks. The median survival for evaluable patients was 26.4 weeks. Trimetrexate was well tolerated with manageable myelosuppression as the dose limiting toxicity. Trime- trexate was shown to have activity in nonsmall cell lung cancer. Activity of a new nitrosourea (TCNU) in human lung cancer xenografts. Fergusson RJ, Anderson LE, Macpherson JS, Robins P, Smyth JF. Imperial Cancer Research Fund, Medical Oncology Unit, University Department of Clinical Oncology, Western General Hospital, Edin- burgh EH4 2XCI. Br J Cancer 1988;57:339-42. The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts

Cisplatin, adriamicin and etoposid in lung oat cell cancer

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s34

from untreated small cell lung cancer patients were the most chemosen- sitive for adriamycin, melphalan, vincristine and VP16 compared to the other cell types. In addition, untreated SCLC was more sensitive than non-SCLC to BCNU and cis-platin, while vincristine was the only drug to which treated SCLC was more sensitive compared to the non-SCLC lines. In contrast, no significant differences between the lung cancer types wereobserved for vinblastine. Thus, this panel of lung cancer cells exhibited a drug sensitivity profile paralleling that observed in clinical practice. These results suggest that this lung cancer cell line panel in combination with a relatively simple but reproducible chemosensitivity assay, such as the M’lT assay, has potential for the testing of drug combinations and evaluating new anti-cancer agents in vitro.

Cisplatin, adriamicin and etoposid in lung oat cell cancer. De La Torre MA, Borau MJ, Gonzalez E, Nieto J, Lopez-Lam F. Servicio de Radioterapia y Oncologia de1 Hospital Clinic0 Universi- tario de Valladolid, 47005 Valladolid. Oncologia 1988;11:181-6.

Have been evaluated 23 patients with oat cell carcinoma of the lung afterthreecoursesofchemotherapyinCAVregimen(CDDP60mg/m*, ADM50mg/m2andVP-16120mg/m2x3),fromjanuary’85tofebruary ‘87. After this therapy the limited disease (EL) patients with remission (partial or complete) received consolidated radiotherapy and again chemotherapy until1 ADM tolerance dosis. The extended disease (EE) patients received the same regimen of chemotherapy and radiotherapy only was indicated with paliative and individualiced character. The completeresponse(CR)ratewas60% inELpatientsand431inEE.The partial remission (PR) rate was 30% in cases with EL and 14% in cases with BE. The CR patients has more increasing survival than PRpatients. The toxicity consisted essentially in myelosuppression (Grade I-II of WHO graduation), nausea-vomiting (Grade I-II) and alopecia (Grade III).

Evaluation of fludarabine phosphate in small cell carcinoma. A Southwest Oncology Group study. Rainey JM, Hill JB, Crowley J. Louisiana Slate Universiry Medical Center, Lufayette, LA. Invest New Drugs. 1988;6:45-6.

Fludarabine phosphate was given as a 5 day bolus infection to eleven evaluablepgtientswithrecurrentsmallcelIlungcarcinoma.Patientshad failed on one prior treatment regimen. There were no responses in the eleven evaluable patients. Severe neurofogic toxicity occurred in one patient. Fhidarabine phosphate as given in this protocol was not an effective agent in recurrent small cell lung carcinoma.

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer. Mattson K, Maasilta P, Tammilehto L, Holsti LR, Grove W. Department of Pulmonary Medicine, Helsinki University Cennal HOS- pital, Helsinki 29. Semin Oncol 1988;15(Suppl2):32-7.

To determine the maximum tolerated dose (MTD) of uimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrex- ate in dosages ranging from 3 to 13.5 mg/m*/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m”, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%). leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity in- cluded nausea and vomiting (67%), mucositis (30%). and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cycle- phosphamide was 7.5 mg/m*/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m?day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%). I2 patientsachievedstabledisease(54%),andfivepatientshadprogressive disease. Results suggest that trimetrexate 10.5 mg/m?day in combina- tion with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Clinical response to trimetrexate as sole therapy for nonsmall cell lung cancer. Maroun J. Ontario Cancer Foundation, Ouawa Clinic, General Divi- sion, Orrawa, Onr. KZH 8L6. Semin Oncol 1988;15(Suppl2):17-21.

Trimetrexate glucuronate was evaluated in 70 nonsmall cell lung cancer patients with incurable disease and/or demonstrated progression following surgery/radiotherapy and no prior cytotoxic chemotherapy. Trimetrexate was initially administered at 8 mg/m* intravenously (IV) daily for 5 days and repeated every 3 to 4 weeks with dose adjustments depending on patient tolerance. A median of two courses oftrimetrexate therapy wasadministered(range 1 to 12).Fifty_nine(84%)patientswere evaluable for reswnse. Eleven uatients (19%) achieved a partial re-

Trimetrexate combined with cisplatin or etoposide in the treatment of nonsmall cell lung cancer: A pilot study. Maroun JA, Natale RB, Robert F. Oftawa General Hospiral. Ottawa, On?. Semin Oncol 1988;15(Suppl2):38-40.

Trimetrexate glucuronate in combination therapy with cisplatin or etowside was evaluated in nonsmall cell lunz cancer patients in a pilot, dose escalation study. Trimetrexate was administered intravenously together with 20 mg/m’ cisplatin or 50 mg/m” etoposide for 5 consecu- tive days at an initial dose of 4 mg/m’. Courses were repeated at 3 week intervals with the trimetrexate dosage escalated according to patient tolerance. In the 12 patients treated to date, reversible myelosuppres- sion, consisting of leukopenia and thrombocytopenia, and nonhematol- ogic grade 1 and 2 toxicities were observed. The study is ongoing. The maximum tolerated trimetrexate dosage levels in combination therapy will be established.

. sponse with a median duration of 15.3 weeks. The median time to response was4.6 weeks. Twenty-three patients (39%) had stable disease with a median time to progression of 15.7 weeks. The median survival for evaluable patients was 26.4 weeks. Trimetrexate was well tolerated with manageable myelosuppression as the dose limiting toxicity. Trime- trexate was shown to have activity in nonsmall cell lung cancer.

Activity of a new nitrosourea (TCNU) in human lung cancer xenografts. Fergusson RJ, Anderson LE, Macpherson JS, Robins P, Smyth JF. Imperial Cancer Research Fund, Medical Oncology Unit, University Department of Clinical Oncology, Western General Hospital, Edin- burgh EH4 2XCI. Br J Cancer 1988;57:339-42.

The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts