homoharringtonine and Carcinoma--Squamous-Cell

Four new and clinically relevant antineoplastic natural products are reviewed. Taxol is derived from the bark of the western yew. It promotes the formation of microtubule bundles which deform the cytoskeleton and interfere with mitosis. Although phase II efficacy testing is incomplete, taxol is effective in the treatment of patients with ovarian carcinoma and has some activity in patients with non-small cell lung cancer and melanoma. It remains untested against several other neoplasms. The chief toxicities of taxol are myelosuppression, mucositis, anaphylactoid reactions, and peripheral neuropathy. Homoharringtonine is the most active and abundant of the cephalotaxine esters derived from the genus Cephalotaxus. This agent appears to act at the ribosome to inhibit protein synthesis and has clinical activity in patients with acute myelogenous leukemia. The dose limiting toxicities of homoharringtonine are hypotension and myelosuppression. SKF 104864 and CPT-11 are derivatives of camptothecin which are still in early clinical trials. They are cytotoxic in vitro, acting through an interaction with topoisomerase I to induce DNA fragmentation. The spectra of activity and toxicity of SKF 104864 and CPT-11 are still undefined. All four of these new natural products offer possibilities for clinical activity for patients with a variety of malignancies.

Topics: Adenocarcinoma; Alkaloids; Antineoplastic Agents, Phytogenic; Camptothecin; Carcinoma, Squamous Cell; Chemical Phenomena; Chemistry; Drugs, Investigational; Harringtonines; Homoharringtonine; Humans; Infusions, Intravenous; Irinotecan; Melanoma; Paclitaxel; Phytotherapy; Plant Extracts; Plants, Medicinal; Topotecan

The chemosensitivities of 27 fresh specimens of head and neck cancers were tested with MTT assay to study the practicability and accuracy of the assay for the examination of chemosensitivity in head and neck cancer patients. The chemosensitivities among cancers of different primary sites, pathologic types, histological differentiations, DNA ploidies and estrogen receptors were compared in an attempt to evaluate the choice of anticancer drugs for individual chemotherapy. Eight anticancer drugs: Methotroxate (MTX), Mitomycin C (MMC), fluorouracil (5-Fu), Carboplatin (CBDCA), Pingyangmycin (PYM), Homoharringtonine (HHA), Etoposid (VP16) and Vincristine (VCR) were included. The success rate of MTT assay in the present study was 92.6% and the accuracy was relatively high. The sensitivity sequence was PYM > HHA > MTX > CBDCA > MMC > 5-Fu > VCR > VP16, which suggested HHA should be recommended first to the chemotherapy of head and neck cancer. No chemosensitivity differences were found among different primary sites histological differentiations and estrogen receptors. The chemosensitivity of squamous cell carcinoma was significantly higher than that of adenoid cystic carcinoma. The chemosensitivity of aneuploid tumor was significantly higher than that of diploid.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Bleomycin; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Drug Screening Assays, Antitumor; Female; Harringtonines; Head and Neck Neoplasms; Homoharringtonine; Humans; Male; Methotrexate; Middle Aged

Eighteen patients entered this study of the efficacy of homoharringtonine (HHT) treatment in advanced squamous cell carcinoma of the head and neck (SCCHN). Seventeen eligible patients received at least one day of the first 5-day cycle of HHT (4.0 mg/m2/day) by continuous IV infusion. Cycles were scheduled to repeat every 28 days. The major severe toxicities encountered were hypotension and myelosuppression. There was one drug-related death. Fourteen patients were evaluable for response, and no patient exhibited an objective response to treatment with HHT.

Topics: Adult; Aged; Alkaloids; Carcinoma, Squamous Cell; Drug Evaluation; Female; Harringtonines; Head and Neck Neoplasms; Hematologic Diseases; Homoharringtonine; Humans; Infusions, Intravenous; Male; Middle Aged