Phase II Study of Mitoxantrone in Patients With Non-Small Cell Lung Cancer

A phase II study of mitoxantrone was performed in 24 patientswith non-small cell lung cancer (NSCLC). Mitoxantrone was administeredby intravenous drip infusion of 12 mg/m² every three weeks.There were no responders among the 21 evaluable patients includingfive patients without prior therapy. The major hematologicaltoxic effect was leukocytopenia. Thrombocytopenia and decreasein hemoglobin were slight. A change in the electrocardiogramwas observed in one patient and one patient experienced cardiogenicshock. Mitoxantrone is not acceptable for the treatment of NSCLC becauseof its low antitumor activity, and careful observation is neededfor administration of this agent to patients with pre-existingrisk factors, such as prior anthracycline exposure, mediastinalradiation or underlying cardiovascular disease.     

The Protective Effect of 2-Mercapto-Ethane Sulfonate (MESNA) on Hemorrhagic Cystitis Induced by High-Dose Ifosfamide Treatment Tested by a Randomized Crossover Trial

High-dose ifosfamide (one or two courses of 6 g/m²) with orwithout mesna was administered to 13 patients with advancednon-small cell lung cancer. The protective effect of 2-mercapto-ethanesulfonate (mesna) against the urotoxic side effects inducedby ifosfamide was examined by a randomized crossover trial.A significant reduction in the incidence of hematuria was observedin the patients receiving mesna. Macroscopic hematuria was observedin only one patient who received treatment with mesna versusseven patients treated with ifosfamide alone. Other symptoms,such as frequency and dysuria, tended to be diminished in thepatients receiving mesna, although the difference was not statisticallysignificant. Our results suggest that mesna is effective inpreventing or diminishing ifosfamide-induced hemorrhagic cystitis.Concomitant use of mesna should allow the administration ofa high dose of ifosfamide although more extensive studies areneeded to define the optimal dose and schedule of administrationof mesna to prevent or attenuate the hemorrhagic cystitis.     

Preliminary Phase II Study of Adriamycin (ADM) in Patients with Non-Small Cell Lung Cancer (NSCLC)

A phase II study of adriamycin (ADM) (60 mg/m² was performedin 22 patients with non-small cell lung carcinoma (NSCLC). Therewere no responders in the 19 evaluable patients (16 with adenocarcinoma,two with squamous cell carcinoma and one with large cell carcinoma).The major side effects were alopecia (89%), leukocytopenia (73%),thrombocytopenia (58%) and upper gastrointestinal symptoms. Although ADM at 60 mg/m² did not appear to have sufficient antitumoractivity against NSCLC in this study, it is necessary to evaluatefurther the efficacy of ADM against NSCLC with another treatmentschedule.     

Phase II Study of UFT in Patients With Advanced Non-Small Cell Lung Cancer

A phase II study of UFT (a mixture of uracil and tegafur; molarratio of uracil to tegafur = 4) was undertaken in 21 patientswith advanced non-small cell lung cancer (NSCLC). UFT was administeredorally at a dose of 400 mg/m² every day, for more than fourweeks. Of 16 adequately treated patients, one (6.3%) showed a partialresponse. Toxic effects included minimal myelosuppression, anorexia,nausea, vomiting and epigastralgia. Gastrointestinal toxicitywas well tolerated. Considering the poor response and mild toxicity,a further phase II study of higher-dose UFT is necessary forpatients without prior therapy.     

Antiemetic Efficacy of High-Dose Intravenous Metoclopramide and Dexamethasone in Patients Receiving Cisplatin-Based Chemotherapy: A Randomized Controlled Trial

High-dose intravenous (IV) metoclopramide has shown efficacywith few side effects for the treatment of nausea and vomitingon the day of cisplatin administration. From November 1984 toJanuary 1986, two randomized trials in an antiemetic study wereconducted. In trial I, the antiemetic effect of a short courseof high-dose dexamethasone was compared with that of high-dosemetoclopramide in 29 patients with lung cancer receiving chemotherapycon taining cisplatin (80 mg/m² IV) in a randomized controlledtrial. Dexamethasone was given IV at a dose of 16 mg 1/2 hrbefore and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin.Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr beforeand 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emeticcontrol (0–2 episodes of vomiting) during the 24 hr aftercisplatin administration was achieved in 55% (6/11) and 67%(12/18) of the patients receiving dexa methasone and metoclopramide,respectively, without serious toxicity. The dura tion of nauseaor anorexia was similar for the two treatment groups. In trial11, the combination of metoclopramide and dexamethasone wascompared with metoclopramide alone to assess the additive antiemeticeffect of the two drugs in 23 patients with lung cancer receivingcisplatin at a dose of 120 mg/m IV in a randomized cross-overstudy. A major antiemetic response was observed in 27% (3/11)and 92% (11/12) of the patients receiving metoclopramide aloneand metoclopramide plus dexamethasone, respectively (p <0.005). The duration of nausea and anorexia was similar forthe two treatment groups. Pa tients tended to prefer the combinationof metoclopramide and dexamethasone; however, the differencewas not statistically significant (p = 0.14) in the small numberof patients entered in this study. Despite excellent controlof acute chemotherapy-induced emesis, 45% of 52 patients experienceddelayed nausea and vomiting more than 24 hr after cisplatinadministration even among those who had had an excellent short-termresponse to the antiemetic agents.     

Unusual cutaneous manifestations of myelodysplastic syndrome

We report a 58-year-old patient with acute myeloid leukaemia who developed an oedematous erythema resembling Sweet's syndrome, accompanied by atypical erythema nodosum and bullous pyoderma gangrenosum. Examination of skin biopsies showed dense infiltration with mature neutrophils. although there was peripheral blood leucocytopenia. The oedematous erythema worsened after he was treated with granulocyte-colony-stimulating factor (G-CSF), which was given For his leucocytopenia. We suggest that when a neutrophilic dermatosis complicates leukaemia, alternatives to G-CSF should be considered for the treatment of leucocytopenia. Corticosteroids were very effective in controlling the skin lesions in our patient.     

Recurrence of Thymoma with Appearance of Myasthenia Gravis 18 Years after Surgery: A Case Report

A 59-year-old woman was admitted to the hospital because ofrecurrence of thymoma with appearance of myasthenia gravis 18years after excision of an invasive thymoma. Recurrence wasobserved in the anterior mediastinum, right pleura, pericardiumand left supraclavicular lymph node. Hashimoto's thyroiditis,vitiligo vulgaris and leukopenia were also seen. After creationof a pericardial window for pericardial effusion, she receivedvincristine, then carbazilquinone intravenously as single chemotherapeuticagents based on the chemosensitivity by clonogenic assay ofthe supraclavicular tumor, but response was not achieved. Atone and a half years after radiotherapy to the mediastinum,she is now doing well without symptoms and is receiving a fairlylow dose of anticholinesterase medication.     

The Incidence of Cardiac Metastasis in Primary Lung Cancer and the Management of Malignant Pericardial Effusion

The incidence of metastasis to the heart and pericardium was35% in post-mortem studies of 150 cases of carcinoma of thebronchus. Twenty-one patients with malignant pericardial effusion fromcarcinoma of the bronchus were treated at the National CancerCenter Hospital during the last three years. Fifteen patientswere treated by creating a pericardial window through a subxiphoidapproach without complications or mortality, in these 15 patientscardiac compression caused by pericardial effusion was promptlyrelieved by the creation of the pericardial window. There wasno reaccumula tion of the effusion in five of six patients treatedby the pericardial window procedure with intrapericardial instillationof chemotherapeutic agents and eight of nine patients treatedby creating the window without local chemotherapy. On the otherhand cardiac tamponade was controlled in one of three patientsby repeated pericardiocenteses. The median survival periodsfrom the initiation of treatment for the effusion up to deathwere 4 mo in six patients treated by the pericardial windowprocedure with intrapericardial instillation of chemotherapeuticagents, 2 mo in nine patients treated by the window techniquewithout local chemotherapy and 0.8 mo in six patients in whoma pericardial window was not created. The median survival of15 patients treated by the pericardial window procedure (2 nio)was not significantly longer than that of six patients not sotreated. We have come to the conclusion that the creation of a subxiphoidpericardial window is a safe, effective and reliable treatmentprocedure for the manage ment of malignant pericardial effusion,but the prognosis for survival in patients with malignant pericardialeffusion may depend principally on the extent of the primarytumor and the performance status of patients at the initiationof treatment for the effusion.     

Phase II Study of 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW2083) in Patients with Advanced Non-Small Cell Carcinoma of the Lung and Metastatic Pulmonary Tumors

Twenty-six patients with non-small cell carcinoma of the lungand 25 with metastatic pulmonary tumors were treated by intravenousinjection of 7-N-(p-hydroxyphenyl)-mitomycin C (KW2083), a derivativeof mitomycin C, either at a single 70-mg/m² dose or at a doseof 20–30 mg/m² once a week for 3 weeks. Two patients withadenocarcinoma among 21 evaluable patients with non-small cellcarcinoma of the lung, and one with embryonal cell carcinomaamong 21 patients with metastatic pulmonary tumors achievedpartial response lasting 5 to 7 weeks. In these three patients,KW2083 was administered by a single 70-mg/m² dose, and no patientswho received a dose of 20–30 mg/m² weekly achieved objectiveresponse. Myelosuppression, primarily thrombocytopenia, waspronounced with either treatment regimen and it was the majordose-limiting toxicity.