The role of the laser in the detection and treatment of tracheobronchial malignant lesions.
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Biomedical subjects
Publications and source records attributed to R T Eagan.
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Twelve patients with a tissue diagnosis of malignant mesothelioma were treated with combination chemotherapy (CAMEO) every 4-5 weeks, with or without hemithoracic radiation. Mean survival from the time of tissue diagnosis an start of protocol treatment was 15.7 and 12.6 months, respectively. Median survival from the time of tissue diagnosis and start of protocol treatment was 11 and 6.5 months, respectively. Two patients were long-term survivors (32 and 45 months), one of whom is alive without evidence of recurrent disease. Toxicity from this regimen was moderate.
Pilot studies to obtain drug dosages for the combinations of dibromodulcitol (DBD) and BP-16, DBD and AMSA, and DBD, VP-16 and AMSA were carried out to levels of acceptable clinical toxicity. Myelosuppression was the dose-limiting toxicity in all combinations. While regressions were few in this group of heavily pretreated patients, we feel the drug combinations need further study in central nervous system, breast, and lung cancers.
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Dianhydrogalactitol was administered as two 1-hr infusions separated by a 4-hr period once every 5 weeks to 21 patients with advanced solid tumors. Total doses ranged from 100 mg/m2 (50 mg/m2 twice on a single day) to 160 mg/m2 (80 mg/m2 twice on a single day). Peak concentrations of drug at the end of a 1-hr infusion ranged from 1.9 to 5.6 microgram/ml. Plasma elimination of dianhydrogalactitol was approximated best by a two-compartment open model. The alpha-half-life was 3.9 +/- 1.9 mins and the beta-half-life was 31.3 +/- 2.7 mins. Dose-limiting hematologic toxicity was encountered at a total dose of 160 mg/m2, with leukopenia occurring more frequently than thrombocytopenia. Other toxic effects included mild to moderate nausea in most patients and two instances of moderate alopecia. One patient with large cell cancer of the lung had a partial regression lasting 2 months and one patient with a carcinoid in the thymus had a partial regression lasting 7 1/2 months. A third patient with a mixed adenocarcinoma-squamous cell carcinoma of the lung had improvement (30% decrease) in his pulmonary tumor for greater than 2 months.
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Sixty-six patients were entered into a prospective, randomized clinical trial evaluating the use of alternating noncross-resistant chemotherapy in patients with extensive small cell carcinoma of the lung. Sixty-five were evaluable. One regimen utilized cyclophosphamide, VP-16, vincristine, cisplatin alternating with doxorubicin (Adriamycin) and DTIC (CVVP-AD). The second regimen utilized doxorubicin, VP-16, vincristine, and cisplatin alternating with cyclophosphamide and DTIC (AVVP-CD). There was no statistically significant difference between the two chemotherapeutic programs in terms of regression rate, time to progression, or survival. Overall regression rate for CVVP/AD was 91% (29/32) including five complete regressions (CRs). For AVVP-CD, the total regression rate was 82% (27/33) including nine CRs. Combined, the overall regression rate was 86% with a CR rate of 22%. Time to progression for CVVP-AD and AVVP-CD was 28 and 26 weeks, respectively. The median survival time of CVVP-AD and AVVP-CD regimens was 40 and 42 weeks, respectively. Prognostic variables significantly correlated with survival were performance score and extensive liver metastases at diagnosis. Correlations between initial sites of disease led to the observation that patients with no central nervous system (CNS) metastases at diagnosis were more likely to have more extensive liver and lung involvement. Further analysis revealed the lung to be the most common site of first progression (46%) and liver second (28%). Patients with extensive involvement of the liver or lung progressed sooner in these sites than those with a lesser tumor extent. At some point in the study, 40% of the patients experienced CNS metastases. The efficacy of these two alternating regimens is comparable to most current regimens reported in extensive SMCLC. Whether cyclophosphamide or doxorubicin is used first seemed to make little difference. The alternate noncross-resistant regimen was rarely effective in producing tumor regression following initial progression.
The drug combinations of dianhydrogalactitol and VP-16 and dianhydrogalactitol, VP-16, and triazinate were used in patients with primary brain tumors, principally astrocytoma, recurrent following cranial irradiation. Tumor regressions were noted in 40% of patients treated with the 2-drug regimen and in 33% of patients treated with the 3-drug regimens. Regression were noted in all grades of tumor. Poor performance score on the patients' part did not seem to effect regression rates. Myelosuppression was the principal toxicity encountered. Dianhydrogalactitol-based combination chemotherapy seems as active as nitrosourea therapy and presents an alternative to nitrosourea therapy.
In a phase I study, a monthly regimen of dianhydrogalactitol 60 mg/m2 X 1 day, VP-16-213 60 mg/m2 X 3 days, and cis-platinum 20 mg/m2 X 3 days produced clinically acceptable toxicity. The program is suitable for outpatient administration and may have a role in the management of selected patients with advanced cancer.
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Thirty patients with previously untreated limited small-cell lung cancer were treated in a prospectively randomized trial comparing chemotherapy versus chemotherapy plus prophylactic whole brain radiation therapy. Without preplanned thoracic radiation therapy in addition to the chemotherapy, 78% of patients failed in the lung (52% in the lung solely) as the first site of treatment failure. In those patients not receiving prophylactic whole brain irradiation, 73% failed in the CNS at the time of first and second failure versus 13% of the group randomized to prophylactic whole brain radiation therapy (and those two before the radiation was given). A strong case can be made for the use of both preplanned thoracic and prophylactic whole brain radiation therapy in conjunction with combination chemotherapy, at least until much more effective chemotherapy is found.
Sixty-two patients with previously untreated limited stage small cell lung cancer were treated in a prospectively randomized trial comparing thoracic irradiation plus combination chemotherapy with VP-16-213, vincristine (Oncovin), cyclophosphamide, and Adriamycin (VOCA) or those same four drugs plus low-dose (40 mg/m2) cisplatin (VOCAP). The addition of the cisplatin in eight courses of planned chemotherapy did not significantly improve either time to tumor progression of survival or alter sites of disease progression. It did, however, worsen the degree and frequency of nausea, vomiting, and myelosuppression. We did not identify any benefit from the usage of low-dose cisplatin as employed in this study.
One-hundred nine patients with limited-stage unresectable non-small-cell lung cancer were treated with Adriamycin--cisplatin-based combination chemotherapy and thoracic irradiation. Of this number, 73 received chemotherapy (one course) prior to irradiation and 37% (27/73) had tumor regression following chemotherapy alone. Sixty-eight percent of patients (73/107) experienced tumor regression following combined chemotherapy and irradiation. Age more than 65 years, a malignant ipsilateral pleural effusion, and no response to chemotherapy alone were all strong negative prognostic factors. Three-year survivals were as follows: all 109 patients, 14.0%; 89 patients without malignant pleural effusion, 17.0%; 71 patients with neither a malignant pleural effusion nor malignant ipsilateral supraclavicular adenopathy, 23.1%.
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A phase II study utilizing VP-16 and adriamycin in a randomized fashion tested the concept of synchronization of the drugs in treatment of metastatic breast cancer. Although there was a trend in median survival following the synchronized schedule, there was no significant difference in survival or progression-free intervals. The concept of synchronization was not established.
Fifty-four patients with metastatic lung cancer were treated with AMSA. Patients with a performance score of 0-1, no prior chemotherapy, and normal liver function received a dose of 35 mg/m2/day iv for 3 days every 4 weeks; patients with a performance score of 2-3, any prior chemotherapy, or abnormal liver functions received a dose of 30 mg/m2/day on the same schedule. Among 53 evaluable patients, responses were noted in one with adenocarcinoma and in two with squamous cell carcinoma (overall response rate, 6%). We conclude that AMSA has limited activity in lung cancer when used in this schedule except perhaps in previously untreated squamous cell carcinoma. Only a limited number of patients with large cell or small cell carcinoma were treated.
Forty-one patients with advanced squamous cell lung cancer and no prior chemotherapy were entered in a prospectively randomized trial comparing dianhydrogalactitol plus Adriamycin (DA) versus DA plus cis-dichlorodiammineplatinum(II) (DAP). The DAP regimen was superior to the DA regimen in regression rate (53% versus 27%), median regression duration (255 versus 122 days), median time to tumor progression (approximately 175 versus 58 days), and median survival time (185 versus 126 days). Patients who were greater than 60 years old responded particularly well to the DAP regimen and accounted for most of the survival advantage. Nausea, vomiting, and myelosuppression were more frequent and severe with the DAP regimen. This study seems to indicate a role of cis-dichlorodiammineplatinum(II) in patients with advanced squamous cell lung cancer. The particular advantage noted for older patients needs further evaluation.