We discuss alternative strategies to develop the chemotherapeutic agent based on targeting ErbB family ligands rather than their receptors. A phase I study of CRM197 for advanced ovarian cancer has already begun, which is the first approved trial of ErbB-ligand-targeted therapy. We also discuss clinical adaptations based on combination of CRM197 with other conventional chemotherapeutic agents.
A new drug dosage form comprising activated carbon particles adsorbing mitomycin C (MMC-CH) is designed to slowly release its components, and has affinity for the tumor surface and lymph nodes and a tendency to stay long in the local portion. The therapeutic index of MMC-CH in experimental carcinomatous peritonitis is 3.1 times as high as that of MMC-solution. In clinical experiments 81 patients with carci-nomatous effusions were administered with MMC-CH (2.0-2.4 mg/kg in terms of MMC) in bolus in-tracavitarily. Fifty-one patients responded well to the MMC-CH therapy. Nineteen patients were alive for more than 6 months. The responders showed marked improvement in subjective symptoms, and 26 patients became dischargeable from hospital. Bone marrow suppression and peritoneal irritation were main adverse effects, but the symptoms were temporary and not so serious in spite of a high dose of MMC. Cancer 59:245-251, 1987. OR CARCINOMATOUS peritonitis or pleuritis, many F kinds of anticancerous agents in solution form have been administered intracavitarily. These methods are not always successful to control the local lesion, because therapeutic agents injected intracavitarily in solution form are easily absorbed through the large serosal surface into blood plasma and it is difficult to keep a high concentration of the agents for a long time in the ~ a v i t y. ~ To surmount this difficulty we have decided to utilize the functional slow-releasing ability of adsorbents, and devised a new dosage form, called MMC-CH,6 comprising fine activated carbon particles adsorbing mitomycin C (MMC). Experiments with animals have shown that MMC-CH slowly releases its components, and has affinity for the tumor surface and lymphatics, and a tendency to stay long in the cavity. Rat experiments indicate that MMC-CH has higher therapeutic effects on experimental carcinomatous peritonitis than MMC-solution.
Primary sarcoma of the fallopian tube is a very rare neoplasm. We report the case of a 69-year-old woman affected with leiomyosarcoma of the left fallopian tube. Her chief complaint was lower abdominal pain. The preoperative diagnosis was a left adnexal malignant tumor based on pelvic examination, abdominal computed tomography, and magnetic resonance imaging. Following a laparotomy, she was ultimately diagnosed with a FIGO IIc fallopian tube leiomyosarcoma. She was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, partial omentectomy, and low anterior resection for rectal invasion. The patient subsequently received adjuvant chemotherapy with pirarubicin and ifosfamide. Thirty months after the first therapy, a computed tomography scan revealed metastasis of the liver, lung, and supraclavicular lymph node. The patient died of the disease 39 months after the initial treatment.
BackgroundBK-UM (CRM197) is a mutant form of diphtheria toxin and a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF). We assessed the safety, pharmacokinetics, recommended dose, and efficacy of BK-UM in patients with recurrent ovarian cancer (OC) or peritoneal cancer (PC), and measured HB-EGF levels in serum and abdominal fluid after BK-UM administration.MethodsEleven patients with advanced or recurrent OC or PC were enrolled and treated with BK-UM via the intraperitoneal route. The dose was escalated (1.0, 2.0, 3.3, and 5.0 mg/m2) using a 3 + 3 design.ResultsEight of 11 patients completed treatment. No dose-limiting toxicity (DLT) was experienced at dose levels 1 (1.0 mg/m2) and 2 (2.0 mg/m2). Grade 3 transient hypotension as an adverse event (defined as a DLT in the present study) was observed in two of four patients at dose level 3 (3.3 mg/m2). Treatment with BK-UM was associated with decreases in HB-EGF levels in serum and abdominal fluid in seven of 11 patients and five of eight patients, respectively. Clinical outcomes included a partial response in one patient, stable disease in five patients, and progressive disease in five patients.ConclusionsBK-UM was well tolerated at doses of 1.0 and 2.0 mg/m2, with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m2 BK-UM is recommended for subsequent clinical trials.Trial registrationThis trial was prospectively performed as an investigator-initiated clinical trial. The trial numbers are UMIN000001002 and UMIN000001001, with registration dates of 1/30/2008 and 2/4/2008, respectively. UMIN000001001 was registered as a trial for the continuous administration of BK-UM after UMIN000001002.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3071-5) contains supplementary material, which is available to authorized users.
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