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悪性胸膜中皮腫には国際的に認められる統一した病期分類法がないため, Intemational Mesothelioma Interest Group (IMIG) は新たに国際中皮腫TNM分類 (IMIG分類) を提案した. 本邦においてよく用いられるButchart分類をはじめとする従来の分類法の殆どはTNM systemに準拠しないで臨床病期を4期に分けている. TNM systemに準じているのはChahinian分類, UICC分類である. 従来の分類法は胸壁浸潤, リンパ節転移の規定が曖昧であり, また, I期の腫瘍進展範囲を広く設定しているため予後を一致させた患者分類が難しい. IMIG分類ではI期を臓側胸膜腫瘍巣の有無により2群に分け, ともにリンパ節転移のないものとしている. N因子は他の中皮腫TNM分類と同様に非小細胞肺癌と基本的に同じであるがprospectiveな確認はされていない. IMIG国際分類は従来のものより的確であり臨床に即している.

Two hundred forty-seven patients with previously untreated nonresectable non-small cell lung cancer (NSCLC) were entered in a prospective, randomized Phase II trial. Response assessment was possible in 232 patients, and 237 patients were evaluable for survival. Thirteen partial responses (11%) and 5 regressions (4%) of evaluable disease were obtained for the 116 patients treated with 5-fluorouracil (5-FU) and cisplatin (C) (95% confidence interval [CI], 8.5% to 21.5%). The median time to progression was 2.2 months and the median survival time was 4.6 months for 5-FU plus C. Twenty-three partial responses (20%) and 4 regressions (3%) of evaluable disease were obtained for the 116 patients treated with 5-FU, C, and vinblastine (V) (95% CI, 15.3% to 30.7%). The median time to progression was 2.8 months and the median survival time was 5.6 months for 5-FU, C, and V. The 5-FU and C doses were equivalent in the two treatment regimens. Sixteen of 85 patients (19%) with a performance status of 0 and 18 of 103 patients (17%) with a performance status of 1 responded, whereas only 2 of 44 patients (5%) with a performance status of 2 or greater responded (P = 0.009). Patients who had received locoregional radiation therapy had a lower overall response rate then those in the no prior radiation therapy group (P = 0.028). The median survival time for patients with a performance status of 0 or 1 was 6.3 months compared with 1.9 months for patients with a performance status of 2 or greater (P less than 0.001). Performance status also appeared to be a significant factor for time to progression. More frequent and severe leukopenia, fever, genitourinary (GU) toxicity, and pulmonary toxicity was reported with 5-FU, C, and V. There were three treatment-related deaths with 5-FU, C, and V and one treatment-related death with 5-FU plus C. Grade III/VI myelotoxicity was not influenced by prior radiation therapy or performance status. Neither regimen is active enough to be considered as standard therapy for advanced NSCLC.

Ten cases of malignant mesothelioma presenting in patients 40 years old or younger at diagnosis were reviewed. Seven cases had a documented history of asbestos exposure of which five were household exposures. The median age at first exposure to asbestos was 10 years and the median duration of exposure was 120 months. The median latency period (time between initial asbestos exposure and diagnosis of malignant mesothelioma) was 19 years. The median interval from initial symptoms to definitive diagnosis was 5.5 months. The case history of each patient is presented. A significant delay in diagnosis in this age group compared with an age-unrestricted series is noted. The significance of nonoccupational exposure to asbestos is emphasized as a probable causative factor in the development of malignant mesothelioma. In addition, a possible genetic predisposition is briefly discussed.

This chapter reviews the clinical features of two types of malignant mesothelioma—pleural and pericardial. Although such distinction refers to the cavity of origin of this neoplasm, it is well known that each of these can spread to the other cavity when tumor progression occurs. In a total of 1496 cases of mesotheliomas reviewed pathologically, Suzuki (1) found the primary site to be pleural in 73.1%, peritoneal in 23.7%, and pericardial in 0.3%. The remainder (2.9%) had multicavitary involvement.

SV40 has been implicated in the etiology of 40% to 60% of human mesotheliomas. These studies could have important medical implications concerning possible sources of human infection and potential therapies if human tumors are induced by this agent. We did PCR-based analysis to detect SV40 large T antigen DNA in human mesotheliomas. None of 69 tumors in which a single copy gene was readily amplified contained detectable SV40 large T antigen sequences. Under these conditions, it was possible to detect one copy of integrated SV40 DNA per cell in a mixture containing a 5,000-fold excess of normal cells using formalin-fixed preparations. Kidney, a known reservoir of SV40 in monkeys, from some of these individuals were also negative for SV40 large T antigen sequences. A subset of mesotheliomas was analyzed for SV40 large T antigen expression by immunostaining with a highly specific SV40 antibody. These tumors as well as several human mesothelioma cell lines previously reported to contain SV40 large T antigen were negative for detection of the virally encoded oncoprotein. Moreover, mesothelioma cell lines with wild-type p53 showed normal p53 function in response to genotoxic stress, findings inconsistent with p53 inactivation by the putative presence of SV40 large T antigen. Taken together, these findings strongly argue against a role of SV40 by any known transformation mechanism in the etiology of the majority of human malignant mesotheliomas.

A patient with malignant mesothelioma experienced tumor recurrence 3 months after pleuropneumonectomy. Samples of the tumor were transplanted into nude mice to assess chemosensitivity. There was close concordance between the results in xenografts and the clinical outcome in this patient. Both mitomycin and to a lesser extent cisplatin were effective as single agents against the nude mouse xenografts, and the combination of these two drugs produced a complete response both in the patient and in the xenografts. The patient survived 18 months from onset of chemotherapy and 24 months from diagnosis. The duration of clinical complete response to chemotherapy was 14 months, despite the fact that mitomycin, the most effective agent against the xenografts, was discontinued after only two cycles because the patient developed pulmonary toxicity. This direct patient-xenograft correlation further validates the usefulness of the nude mouse model in the search for effective therapies for malignant mesothelioma, a tumor characterized by frequent refractoriness to most available agents.

BACKGROUND The purpose of this study was to assess the efficacy and toxicity of a combination of cisplatin and irinotecan (CPT-11) in the treatment of patients with malignant pleural mesothelioma and to characterize the pharmacokinetic profiles of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). METHODS Fifteen previously untreated patients with malignant pleural mesothelioma were treated with cisplatin (60 mg/m2 on Day 1) and CPT-11 (60 mg/m2 on Days 1, 8, and 15) administered intravenously and followed by a 1-week rest period. The course of treatment was repeated every 28 days. After intravenous administration, the levels of CPT-11 and SN-38 in the plasma and pleural fluid were determined for each histologic subtype of mesothelioma. RESULTS All patients were evaluable for response and toxicity. Four partial responses (response rate of 26.7%) with a median response duration of 25.9 weeks and 2 regressions of evaluable disease (overall response rate of 40%) were observed. The median survival time after chemotherapy was 28.3 weeks, and the median time to treatment failure was 22.1 weeks. The 1-year survival rate for all patients was 38.5%. Toxicity was well tolerated, and there were no treatment-related deaths. World Health Organization Grade 3 leukopenia occurred in 3 patients (20%), and Grade 1 or 2 diarrhea occurred in 3 patients (20%). There was no excess toxicity in patients with large pleural effusions compared with those with no pleural effusions. CPT-11 and SN-38 were detected in the pleural fluid 1 hour after intravenous administration. The maximum concentrations of CPT-11 and SN-38 in the pleural fluid were 36.5% and 75.8%, respectively, of the corresponding plasma values. CONCLUSIONS The combination of cisplatin and CPT-11 had definite activity against malignant pleural mesothelioma and was well tolerated. The intravenous administration of CPT-11 produced adequate distribution of CPT-11 and its active metabolite SN-38 into the pleural fluid and allowed a higher concentration of the more active SN-38 to make contact with mesothelioma cells in the thoracic cavity. These results warrant further clinical evaluation of this combination chemotherapy for the treatment of malignant pleural mesothelioma in a confirmatory Phase II trial. Cancer 1999;85:2375–84. © 1999 American Cancer Society.

Invasive thymomas are usually slowly growing tumors that tend to recur within the thoracic cavity (Le Golvan et al. 1977; Wilkins et al. 1966). The overall 5-year survival varies between 23% and 60% (Batata et al. 1974; Bernatz et al. 1961, 1973; Legg et al. 1965; Namba et al. 1978; Otto et al. 1978; Slater et al. 1978). Approximately one-third of patients with thymoma have myasthenia gravis, and one-tenth of patients with myasthenia gravis have a thymoma (Namba et al. 1978). The presence of myasthenia gravis in patients with thymoma adversely affected survival in some series (Wilkins et al. 1966), but not in others (Bernatz et al. 1973). Surgery and radiotherapy have been the major therapeutic modalities that have been used in the management of invasive thymoma. These modalities are discussed at length elsewhere in the text; however, some points deserve further mention. Repeat thoracotomy for recurrent intrathoracic thymoma is not unusual and adjuvant radiotherapy has been recommended by several authors (Wilkins et al. 1966; Bernatz et al. 1961, 1973; Goldman et al. 1975; Penn et al. 1972; Ariaratnam et al. 1979).

Many patients with diffuse malignant pleural mesothelioma have dyspnea or chest pain. Cardiac symptomatology is frequently difficult to differentiate from symptoms of pleuropulmonary disease. To better define the clinical characteristics of cardiac involvement in patients with mesothelioma, the electrocardiographic (EKG) and echocardiographic findings in 64 patients with biopsy-proven malignant pleural mesothelioma were reviewed. A total of 19/64 (30%) patients had autopsy studies available for review. The EKG was abnormal in 55 patients (89%). Over half (60%) had an arrhythmia, including sinus tachycardia (42%), premature atrial and ventricular contractions (13%), atrial fibrillation (3%), and atrial flutter (1%). Over one third (37%) had a conduction abnormality, including bundle branch block (13%), hemiblock (8.5%), and incomplete right bundle branch block (13%). Echocardiography revealed a total of 13 patients with pericardial effusions, two with pericardial thickening, and one with an anterior sonolucent space. Of 19 autopsies, cardiac invasion was found in 14 (74%), with more than half to the pericardium and more than one quarter to the myocardium. It is concluded that: clinical cardiac abnormalities occur in the great majority of patients with malignant pleural mesothelioma, pathologic cardiac invasion occurs in the great majority of patients with pleural mesothelioma, and the EKG and echocardiogram are helpful in differentiating cardiac involvement from progressive pulmonary disease in patients with pleural mesothelioma.

Two lymphocytic neoplasms, chronic lymphocytic leukemia and poorly differentiated lymphoma, were detected in two patients who had nonoccupational exposure to asbestos. Both had a pleural mesothelioma subsequent to their initial presentation with lymphocytic neoplasm. Recent reports have suggested a possible association between asbestos exposure and lymphoproliferative neoplasms. Chronic antigenic stimulation by asbestos could predispose one to the immunoproliferative disorders seen in these patients. The possible significance of this relationship is discussed for future consideration.

The clinical presentation and therapeutic modalities of 11 patients with invasive or metastatic thymoma are presented. Two patients had myasthenia gravis, and five had extrathoracic metastases. Survival exceeded five years in five patients, and four patients remain free of recurrence between 2.1 and 9.0 years after diagnosis. Surgery, with an attempt at complete resection, is the first step of therapy. A second thoracotomy for local relapse or attempt at curative resection was carried out in four patients. Radiotherapy to the mediastinum and/or metastatic sites was given to ten patients with doses ranging from 3600–6000 rads (median = 4500 rads) in the nine nonmyasthenic patients. Inclusion of supraclavicular fossae in the radiotherapy field is recommended because it was a site of relapse in two patients. Systemic therapies were given to eight patients. Objective responses were seen with two of various chemo-therapeutic regimens. A combination of bleomycin, Adriamycin, cisplatin, and prednisone (“BAPP”) produced a partial remission in two of five patients, during 12 and 4 months, respectively. Two of three patients responded to maytansine as a single agent after failure of other agents. Immunotherapy with intravenous Corynebacterium parvum or intradermal Methanol-Extraction Residue of bacillus Calmette-Guerin (MER-BCG) was ineffective in one patient each. The importance of combined modalities in the management of the disease is emphasized.

Serum concentrations of unhydrolyzed hyaluronic acid (HA) in nude mice bearing human malignant mesothelioma xenografts were determined by size-exclusion chromatography. HA rose to 8-16 micrograms/mL (controls: less than 1 micrograms/mL) by the fourth to fifth day after tumor (epithelial) transplantation, 3 to 5 days before palpability. Decreases in HA during late tumor growth are probably attributed to tumor necrosis, based on the observation that HA was 2.5 times less in necrotic than in viable tumor tissues. This serum biomarker, recognizable before physical detectability of xenografted tumors, should have applicability to monitoring experimental chemotherapy in mice and to early diagnosis and monitoring of human malignant mesothelioma.

The location of autologous serum albumin within the alveolar-capillary membrane was studied in the rat under physiological conditions using antialbumin antibodies labeled with peroxidase. Albumin was detected in the lung interstitium, and in numerous pinocytic vesicles within endothelial cells and type I alveolar epithelial cells. The immunoreaction was also positive at the level of plasmalemmal membranes of both cell types and in the alveolar lining material.

Liver cell ultrastructure was studied in 6 adult patients with α1-antitrypsin (AAT) deficiency (Pi phenotype ZZ); all except 1 were suffering from severe pulmonary emphysema; the liver was histologically normal in 3 patients, and portal fibrosis or cirrhosis was present in the other 3. Conventional electron microscopy showed specific changes consisting of deposits of an amorphous material in the dilated lumina of the endoplasmic reticulum; although these changes were demonstrated in all specimens, the number of liver cells showing these abnormalities varied markedly with each patient; the other liver cells were normal or were affected by nonspecific changes consisting mainly of an increased number of lysosomes; the liver cells with these nonspecific changes were present only in the patients with liver fibrosis or cirrhosis. Electron microscopy, combined with the use of anti-AAT antibodies labeled with horseradish peroxidase, demonstrated that a material antigenically similar to AAT was present in the deposits and on the ribosomes of the endoplasmic reticulum of those liver cells with the specific ultrastructural changes. It is concluded that in patients with AAT deficiency: (1) a material antigenically similar to AAT is synthesized by the ribosomes, but, for unknown reasons, is not exported or is poorly exported into plasma and accumulates in the lumina of the endoplasmic reticulum; (2) the nonspecific ultrastructural changes, associated with, and presumably leading to, liver fibrosis and cirrhosis, are not directly related to the accumulation of this material in the liver cells.

A 46-year-old patient who developed a right pleural mesothelioma 18 years after asbestos exposure was found to have diffuse reticular nodular infiltrates in both lungs. Lung biopsy by fiberoptic bronchoscopy revealed alveolar and interstitial spread of the neoplastic cells. A dramatic clinical and radiologic response occurred after treatment with a combination of doxorubicin (Adria-mycin) and 5-Azacytidine. Cancer 42:1687–1691, 1978.

A 69-year-old woman was admitted to the hospital because of recurrent cervical nodules, a large anterior mediastinal mass, and malignant left pleural effusion. Light and electron microscopy of the resected cervical nodules and cytology of the pleural fluid showed findings consistent with parathyroid carcinoma. There was no evidence of hyperparathyroidism on clinical evaluation, multiple serum calcium and phosphorus determinations, skeletal survey, intravenous pyelogram, or radioimmunoassay of intact and carboxyl-terminal parathyroid hormones in the serum. Electron microscopy revealed secretory granules in the cytoplasm of malignant cells. A dramatic and complete resolution of the mediastinal mass and pleural effusion occurred after 18 months of chemotherapy with "MACC" (methotrexate, adriamycin, cyclophosphamide and CCNU).

Eighty-three patients (53 men, 30 women) with advanced lung cancer were treated with a four-drug combination (MACC) consisting of methotrexate, adriamycin, cyclophosphamide and CCNU given once every 3 weeks. The overall objective response rate (complete response and partial response >50%) was 52% with a median duration of therapy of 29 weeks. Response rate was highest for small cell carcinoma (87%) followed by adenocarcinoma (58%) and squamow cell carcinoma (36%). There was a significant prolongation of median survival for responders vs. nonresponders: 48 weeks vs. 17 weeks for the whole group (p < 0.005), 48 weeks vs. 19 weeks for small cell carcinoma, 48 weeks vs. 15 weeks for adenocarcinoma, 40 weeks vs. 20 weeks for squamous cell carcinoma, and 56 weeks vs. 17 weeks for large cell carcinoma. Prolongation of survival was also apparent when analyzed by extent of the disease (limited vs. extensive) and by performance status. Major toxic effects included bone marrow depression (leukopenia in 36 and thrombocytopenia in 12 patients), mucositis (13 patients), fever and/or sepsis (11 patients), renal toxicity (4 patients) and skin rash (4 patients). There was only one case of cardiotoxicity, and one treatment-related death from septic shock during leukopenia. This regimen has shown activity in all cell types of lung cancer and is easy to administer on an out-patient basis. Cancer 43:1590- 1597, 1979. NCOURAGING RESULTS have recently been E achieved in the chemotherapy of small cell bronchogenic carcin~ma.~ The other cell types of lung cancer remain, however, much more refractory to the action of presently available drugs. Following favorable preliminary result^,^,^ the present report summarizes a three-year experience with a fourdrug combination-methotrexate, adriamycin, cyclophosphamide and CCNU (MACC) -in patients with advanced lung cancer.

In order to evaluate the mechanisms which facilitate the transfer of 67Ga from transferrin in plasma to intracellular binding sites, lactoferrin, a glycoprotein with high affinity for 67Ga, was used as a probe to study the effect of protein binding on gallium uptake by tumor cells. The in vivo effect of transferrin and lactoferrin on the biodistribution of 67Ga was studied in nude mice bearing human malignant mesothelioma. Tumor uptake of 67Ga was reduced 30% by transferrin and 57% by lactoferrin compared with 67Ga-citrate alone. Liver uptake of 67Ga, however, was significantly increased by binding to lactoferrin. The in vitro binding of 67Ga to tumor cells (Burkitt's lymphoma) was apparently promoted by the addition of transferrin or lactoferrin to the incubation medium, but this glycoprotein enhancement of gallium uptake by the cells was dependent on the albumin level, decreasing in absolute uptake as the albumin concentration was increased, suggesting nonspecific binding of glycoproteins to cells. Because of the significant amount of nonspecific binding of 67Ga-labeled glycoprotein complexes in cell culture experiments, in vitro experiments should be used with caution in developing a hypothesis on the mechanisms of cellular uptake of radiogallium. In vivo experiments suggest different mechanisms for cellular uptake of 67Ga in neoplastic tissue and in liver.

An unusual case of small cell anaplastic carcinoma of the lung, presenting as a pelvic mass, is presented. Histochemical and electron microscopic findings confirmed the diagnosis. The pathologic features and unique clinical characteristics are discussed with comments on the topic of metastatic ovarian tumors.

Variations in the dimensions of 65 bronchogenic epidermoid tumors of known spontaneous doubling time were studied under the influence of four chemotherapeutic regimens: cyclophosphamide, 19 cases; Mitomycin C, 20 cases; CCNU, 9 cases; and a five-drug combination, 17 cases. Several parameters were measured, and escape was defined as the moment in time when the growth curve during treatment became parallel to the spontaneous growth curve. The parameters measured were nature and distribution of responses (unchanged progression, slowing-down, plateau, regression), duration of response, time required to achieve maximum response, and time lapse between maximum response and escape. Regarding application to lung cancer, we have concluded from our results that Mitomycin C should replace cyclophosphamide in combination chemotherapeutic regimens. With regard to general strategy, our results suggest that the drug regimen should be changed as soon as maximum response is reached or immediately following the first course if progression continues unchanged. Moreover, in all of the 27 patients whose tumors regressed, escape occurred within less than three months from the onset of the treatment. In view of this fact and insofar as chemotherapy is considered for adjuvant therapy aiming at complete eradication, sequential combinations would be preferable to prolonged administration of a single agent or combination.

The treatment of patients with small cell carcinoma of the lung (SCCL) with combination chemotherapy and radiation has dramatically improved survival in the past decade. With this increased survival, long term complications of therapy are becoming apparent. We report a patient who died of acute myelogenous leukemia (AML) while in complete remission from SCCL. Review of the literature indicates that there may be an increased incidence of AML following successful induction of complete remission in patients with SCCL.

In samples of 16 surgically resected mesotheliomas arising from the pleura of the human lung, 6 enzymes from different metabolic pathways, DNA, and mitotic frequency were quantified. The mesotheliomas, irrespective of cell type or grade, showed lower gamma-glutamyl transpeptidase (GGT) concentration than 36 of the 38 pulmonary adenocarcinomas. The mean concentration of this enzyme in the 15 mesotheliomas was an eighth of that in the 56 carcinomas, whereas their DNA content was similar. The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas. As estimated from their TK [and its recently established quantitative correlation to volume doubling time (DT)], the DT of the 16 mesotheliomas ranged from 50 to over 700 days, with a somewhat longer median than the median for pulmonary carcinomas. Subject survival, though shortest for the 2 sarcomatous mesothelioma cases, varied over an overlapping range for mesotheliomas with epithelial or mixed cell type. The biopsy samples' TK and UK concentrations, however, showed a significant inverse correlation with months of survival after diagnosis. Survival time after the first appearance of symptoms decreased linearly (on log scales) with TK concentration (P less than .001) over the 14 cases. The results of this first quantitative study of a spectrum of biochemical constituents of mesotheliomas identify GGT as an enzyme whose measurement guards against mistaking mesotheliomas and adenocarcinomas for one another and show that the TK concentrations of these mesothelioma samples bear a highly significant, inverse correlation to the postdiagnosis survival time of the individual subjects.

We conducted a prospective, randomized study to clarify the role of radiotherapy of the primary tumor in limited small-cell cancer of the lung. After stratification for sex and for performance score based on the ability to ambulate, patients were randomly assigned to receive initial radiotherapy plus chemotherapy, delayed radiotherapy plus chemotherapy, or chemotherapy alone. The chemotherapy consisted of cyclophosphamide, etoposide (VP-16-213), and vincristine, with doxorubicin subsequently replacing etoposide in alternate cycles 7 through 18. Chemotherapy was given every three weeks for 18 months. The radiotherapy comprised 4000 rad in four weeks, followed by a 1000-rad "boost" directed against residual disease. All patients received prophylactic whole-brain radiation. The patients enrolled totaled 426, and 399 were evaluable. There was a statistically significant difference in the frequency of complete responses in favor of the two radiotherapy regimens (P = 0.0013). Failure-free survival was also longer with these two regimens (P less than 0.001), as was the interval before treatment failure in the chest (P less than 0.001) and overall survival (P = 0.0099). As expected, toxic effects--chiefly neutropenia--were also increased. The addition of radiotherapy of the primary tumor to combination chemotherapy improved both complete-response rates and survival, with increased but acceptable toxicity.

The tumor doubling time (TDT) of 50 measurable pulmonary cancers (primary and metastatic) has been evaluated by the Collins graphic method. The prognosis value of the TDT has been discussed in correlation with some current clinical and laboratory features, ie sex, age, erythrocyte sedimentation rate, tuberculin cutaneous response, size of the tumor on the first roentgenogram, and clinical symptoms. The closest correlation has been found with Feinstein’s symptom staging, which can be applied moreover to every pulmonary cancer, measurable or not.

To the Editor. —In the FebruaryArchivesBukowski et al 1 reported a complete objective response of pulmonary metastases from parathyroid carcinoma following chemotherapy with fluorouracil, cyclophosphamide, and dacarbazine (imidazole carboxamide). They also stated that "reports of chemotherapy for this neoplasm have appeared, but these attempts have been ineffective." We previously reported 2 a case of parathyroid carcinoma with a large mediastinal metastasis and left pleural effusion. That patient was treated with a combination of methotrexate, doxorubicin, cyclophosphamide, and lomustine with complete regression of the mediastinal mass and pleural effusion. The duration of response was 18 months. Our patient did not have hypercalcemia, and that parameter could not be used as a criterion of response. Diagnosis was confirmed, however, by three independent pathologists and by electron microscopy. It is of interest that in our case, as well as in the patient described by Bukowski et al, 1 recurrence of parathyroid

• The diagnosis of Carney's triad requires the coexistence of at least two of three rare disorders, including gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma. Seventeen cases have been reported so far, occurring predominantly in young female patients. We report herein the 18th case of this entity and the first case, to our knowledge, where pulmonary metastases from a gastric leiomyosarcoma coexisted in a patient with benign pulmonary chondromas. (Arch Intern Med1983;143:1462-1464)

A combination chemotherapy (MACC) consisting of methotrexate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, and lomustine (CCNU) was given to 41 patients with stage III bronchogenic carcinoma, 34 of whom had disseminated disease. The objective response rate was 46% for all patients with a median actuarial survival of nine months. Response was seen in all cell types, including four of ten patients with squamous cell carcinoma, six of 17 with adenocarcinoma, and six of seven with small-cell anaplastic carcinoma. Prolongation of survival was apparent for patients of all cell types. Toxic reactions were moderate and allowed for easy outpatient use. ( JAMA 237:2392-2396, 1977)