tnp-351 and Lung-Neoplasms

tnp-351 has been researched along with Lung-Neoplasms* in 4 studies

Reviews

1 review(s) available for tnp-351 and Lung-Neoplasms

ArticleYear
[New analogues of methotrexate].
    Gan to kagaku ryoho. Cancer & chemotherapy, 1992, Volume: 19, Issue:13

    New antifolate antimetabolites are currently developed and three analogues of methotrexate (MTX) (Trimetrexate, Edatrexate, TNP-351) are undergoing clinical trials in Japan. Trimetrexate characteristically enters cells primarily by passive transport, which is different from the mechanism of MTX. The increased therapeutic efficacy of Edatrexate is expected, because of the higher concentration of polyglutamates than MTX in tumor cells. TNP-351 is a novel antifolate, which has a different chemical structure from other antifolates. The current state of clinical trials of three antifolates and the indications for chemotherapy of lung cancer are reviewed.

    Topics: Aminopterin; Animals; Antineoplastic Agents; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Methotrexate; Trimetrexate

1992

Trials

1 trial(s) available for tnp-351 and Lung-Neoplasms

ArticleYear
[The clinical phase I study of TNP-351. The TNP-351 Research Committee].
    Gan to kagaku ryoho. Cancer & chemotherapy, 1995, Volume: 22, Issue:2

    The clinical phase I study of TNP-351, an antifolate drug having a novel structure, was performed through a multicenter cooperative program in 40 patients with solid tumors. The test drug was used on dosage schedules of single and daily doses for 5 or 3 days (by intravenous drip over 30 minutes, respectively). From the daily administration for 5 days, severe adverse reactions such as myelosuppression, became manifest at 5 mg/m2 (1n). This schedule was then switched to daily administration for 3 days. Administration of the test drug was initiated at a dose of 5 mg/m2. On a single-dose schedule, the dose was increased up to 100 mg/m2 (20 n), and on the 3-day daily administration schedule, up to 10.8 mg/m2 (2.2 n). Consequently, 26 of the study patients received single doses; three of them the 5-day daily administration, and 11 the 3-day daily administration. The dose-limiting factors were leukopenia and thrombopenia on both the single-dose and 3-day daily administration schedules. MTD was 100 mg/m2, and MAD, 75 mg/m2 for the single-dose schedule; and 10.8 mg/m2 and 9 mg/m2 for the 3-day daily administration schedule. WBC and platelet counts fell to nadirs at 1-2 weeks on either the single-dose or 3-day daily administration schedule, and it took the respective parameters about 1 week to recover. Subjective and objective adverse reactions to the test drug consisted of digestive tract disorders manifested as stomatitis, anorexia, nausea and vomiting; and laboratory abnormalities such as elevations of GOT and GPT in addition to the myelosuppression. Many of these adverse reactions subsided within 3 weeks after initiation of TNP-351 treatment. On the single-dose schedule, the test drug occurred chiefly in unchanged form in the blood, and in this form it disappeared from the blood biphasically with an alpha phase of 0.29-0.95 hours, and a beta phase of 7.8-14.4 hours. This disappearance pattern did not vary with an increase in dose. The 24-hour urinary excretion rate of the unchanged form amounted to 42-62% of the administered doses. On the 3-day daily administration schedule, the test drug was not accumulated in vivo. In the present study, two patients with malignant fibrous histiocytoma responded to the test drug with tumor regression. The results suggested that the recommended dosage regimen for the clinical early phase II study of the test drug should comprise a course of 9 mg/m2/day (by intravenous drip infusion over 30 minutes) every day for 3 days, which s

    Topics: Adult; Aged; Anorexia; Antineoplastic Agents; Breast Neoplasms; Drug Administration Schedule; Female; Gastrointestinal Neoplasms; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Methotrexate; Middle Aged; Stomatitis; Vomiting

1995

Other Studies

2 other study(ies) available for tnp-351 and Lung-Neoplasms

ArticleYear
Growth inhibitory effects of antifolates against an adriamycin-resistant human small cell lung cancer cell line.
    Acta medica Okayama, 1997, Volume: 51, Issue:3

    We have established an Adriamycin (ADM)-resistant small cell lung cancer (SCLC) cell line, SBC-3/ADM 100, which shows multifactorial mechanisms of resistance to ADM, such as over-expression of P-glycoprotein, an enhanced detoxifying system and a decrease in topoisomerase II activity. In the present study, we confirmed that SBC-3/ADM 100 showed collateral sensitivity to methotrexate and TNP-351, a new antifolate, though this cell line showed a typical multidrug resistance (MDR) pattern. We also demonstrated a faster uptake and higher accumulation (1.3-fold) of TNP-351 in the SBC-3/ADM 100 cells than those in the parent SBC-3 cells. These results explain one of the mechanisms for collateral sensitivity in the resistant cells. Furthermore, this cell line was found to have no cross-resistance to edatrexate and minimal cross-resistance to trimetrexate, 254-S (cisplatin analog), 5-fluorouacil and 4-hydroperoxyifosfamide. These drugs will have clinical importance in patients with SCLC who were previously treated with an ADM-containing regimen. Thus, antifolates, especially TNP-351 and edatrexate, can be expected to eradicate residual multidrug resistant SCLC cells selected by ADM.

    Topics: Animals; Carcinoma, Small Cell; Cell Cycle; Doxorubicin; Drug Resistance, Neoplasm; Folic Acid Antagonists; Growth Inhibitors; Humans; Intracellular Fluid; Lung Neoplasms; Methotrexate; Rabbits; Tumor Cells, Cultured

1997
Synthesis and antitumor activity of pyrrolo[2,3-d]pyrimidine antifolates with a bridge chain containing a nitrogen atom.
    Chemical & pharmaceutical bulletin, 1995, Volume: 43, Issue:2

    Novel pyrrolo[2,3-d]pyrimidine antifolates (1a, b and 2a, b) with a nitrogen atom in the bridge chain between the 2,4-diaminopyrrolo[2,3-d]pyrimidine and phenylene rings were designed and efficiently synthesized. These compounds exhibited more potent inhibitory activities than methotrexate (MTX) against the proliferation of human epidermoid carcinoma KB cells and human non-small cell lung carcinoma A549 cells despite their modest dihydrofolate reductase (DHFR)-inhibitory potency.

    Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cell Division; Folic Acid Antagonists; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Methotrexate; Microcomputers; Nitrogen; Pyrimidines; Structure-Activity Relationship; Tumor Cells, Cultured

1995