Advanced Bronchogenic Carcinoma Research Articles

A Phase II Study on Lonidamine Combined with Cisplatin and Etoposide in the Treatment of Advanced Non-Small Cell Bronchogenic Carcinoma (NSCBC)

A group of 28 patients with advanced non-small cell bronchogenic carcinoma (NSCBC) entered a phase II study on cisplatin (60 mg/m2, day 1) plus etoposide 120 mg/m2, day 1 to 3), every 3 weeks, in combination with lonidamine (150 mg p.o. t.i.d. continuously from day 1). Seven out of twenty-seven (26%) evaluable patients obtained a partial remission (median duration 22 weeks, range 7-47). Although the side effects were mild, three patients stopped the therapy because of them. Median survival was 14 months, range 2-19. Further studies are necessary to clarify the role of "biochemical modulators" in NSCBC.

Megestrol Acetate in Cachectic Patients with Advanced Bronchogenic Cancer

Megestrol acetate, a semisynthetic gestagen, is effective not only for endocrine therapy of advanced breast carcinoma, but also in treatment of cachectic patients with aggressive, hormone-independent tumors. 40 patients with therapy-resistant, advanced bronchogenic carcinoma of different histologic type, who had lost more than ten percent of their regular body weight within a prospective, non-randomized trial were treated with megestrol acetate at a dose of either 160 mg/day or 480 mg/day for 3-4 months. The average weight gain of all patients was 3.0 kg. Nearly all of them (80%) reported improved appetite and well-being. The weight gain in the group of patients receiving 160 mg/day was higher (80%) than in the group receiving 480 mg/day (50%), suggesting that the lower dose is as effective as the higher one for palliative treatment.

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced squamous bronchogenic carcinoma: A randomized study

Combined radiotherapy and chemotherapy versus radiotherapy alone in locally advanced squamous bronchogenic carcinoma: A randomized study

Laser Photodynamic Therapy for Inoperable Bronchogenic Squamous Carcinoma

Fifteen consecutive patients with advanced squamous bronchogenic carcinoma, most of whom had had radiotherapy, were given palliative photodynamic therapy, using either haematoporphyrin derivative or dihaematoporphyrin ether to light sensitize their tumour. All tumours responded to treatment by subsequent light at 630 nm and in the 12 patients where adequate tumour illumination was achieved there was complete clearing of the bronchus in three and partial (more than 50 per cent clearing) in the remaining nine, with relief of haemoptysis and/or breathing obstruction. One patient with recurrent tumour in a pneumonectomy stump after radiotherapy has remained disease-free for over two years since photodynamic therapy. The main complications were temporary skin light sensitization reaction in three, infection after reaeration of lung tissue in two, and transient but severe worsening of breathing obstruction in two.

Aclacinomycin A. Phase II evaluation in bronchogenic squamous-cell carcinoma.

Aclacinomycin A (ACLA-A) was administered to 22 patients with metastatic measurable bronchogenic squamous-cell carcinoma in a Phase II trial of the drug. Sixteen patients were fully assessable for response and toxicity. The initial dose of ACLA-A was 85 mg/m2 weekly for 4 consecutive weeks; however, due to severe myelosuppression, the weekly dose was reduced to 65 mg/m2. Fifteen patients were previously untreated. Toxicity was primarily hematological. Complete or partial responses were not observed on this treatment schedule. ACLA-A administered on this schedule lacks therapeutic efficacy in the treatment of patients with advanced bronchogenic squamous-cell carcinoma.

Chemotherapy (CT) of advanced non-oat cell bronchogenic carcinoma (NOBC) with cyclophosphamide (C), adriamycin (A), methotrexate (M) and procarbazine (P) (CAMP) vs cis-platinum (D) and etoposide (E) (DE): A randomized study

Chemotherapy (CT) of advanced non-oat cell bronchogenic carcinoma (NOBC) with cyclophosphamide (C), adriamycin (A), methotrexate (M) and procarbazine (P) (CAMP) vs cis-platinum (D) and etoposide (E) (DE): A randomized study

Azygos Lymph Node Enlargement as Initial Manifestation of Underlying Disease

Azygos lymph node enlargement is usually an indication of advanced bronchogenic carcinoma, although it may occur in benign pulmonary disease. Often it is found in conjunction with enlargement of hilar and other mediastinal lymph nodes. Isolated azygos lymph node enlargement is unusual and demands tissue diagnosis. Four patients without other evidence of underlying disease were evaluated because of roentgenographic finding of azygos lymph node enlargement. Three had malignant disease and one reactive lymphoid hyperplasia. Current concepts of mediastinal lymphatic drainage are presented. Because of the likelihood of underlying malignancy, biopsy examination of an enlarged azygos node by cervical mediastinoscopy is indicated.

Ftorafur, Adriamycin and Mitomycin C (FAM II) for Extensive Bronchogenic Adenocarcinoma and Large Cell Carcinoma

Twenty-six patients with advanced bronchogenic adenocarcinoma or large cell carcinoma were treated by combination chemotherapy consisting of Ftorafur, adriamycin and mitomycin C (FAM II). The patients had not received prior chemotherapy and were not eligible for radiotherapy and surgery. The overall response rate was 25% (5 of 20 patients). One patient with adenocarcinoma achieved a complete response, four achieved a partial response and three a minor response. In four patients the disease was stable. The response did not vary strictly with initial performance status as patients with a Karnofsky score of less than 70% also showed a median survival of 7.5+ months. The FAM II combination was very well tolerated, particularly regarding nausea and vomiting; the latter occurred in only one patient. No patient required a reduction in the drug dose because of leukopenia or thrombocytopenia.

Cis-platinum and etoposide combination chemotherapy of advanced non-oat cell bronchogenic carcinoma.

From December 1981 to November 1982, a consecutive series of 37 patients with advanced non-oat cell bronchogenic carcinoma were treated with cis-platinum and etoposide in doses of 20 mg/m2 and 75 mg/m2, respectively, for 5 consecutive days every 3 weeks. Among the 33 evaluable patients, one complete response, 11 partial responses, five minor responses, seven unchanged states, and nine cases of progression were noted. Median duration of response was 30+ weeks. Toxicity was significant, but no treatment-related deaths were encountered. Combined cis-platinum and etoposide can provide significant palliation in approximately one-third of patients with the doses and schedule used.

Vindesine in bronchogenic carcinoma

Twenty-seven patients with advanced bronchogenic carcinoma were treated with vindesine, 3 mg/m2/week. Twenty-three patients were evaluable for response. Two of six patients with small-cell carcinoma and one of 17 patients with non-small-cell carcinoma had partial responses. Two other patients with non-small-cell carcinoma had minor responses. The duration of the responses was 2-4 months. Neurologic toxicity occurred in 14 patients and was mild except in two patients. There was a median hemoglobin fall of 2.2 g/dl and a median leukocyte nadir of 2800/μl during vindesine therapy. Thrombocytopenia occurred in 2 patients and mild thrombocytosis occurred in 10 patients. Seven patients experienced phlebitis or cellulitis at the site of drug administration which could be prevented with small doses of intravenous methylprednisolone. These results suggest that vindesine is well tolerated and possesses some activity in patients with previously treated bronchogenic carcinoma.

Vindesine in bronchogenic carcinoma

Twenty-seven patients with advanced bronchogenic carcinoma were treated with vindesine, 3 mg/m2/week. Twenty-three patients were evaluable for response. Two of six patients with small-cell carcinoma and one of 17 patients with non-small-cell carcinoma had partial responses. Two other patients with non-small-cell carcinoma had minor responses. The duration of the responses was 2-4 months. Neurologic toxicity occurred in 14 patients and was mild except in two patients. There was a median hemoglobin fall of 2.2 g/dl and a median leukocyte nadir of 2800/microliter during vindesine therapy. Thrombocytopenia occurred in 2 patients and mild thrombocytosis occurred in 10 patients. Seven patients experienced phlebitis or cellulitis at the site of drug administration which could be prevented with small doses of intravenous methylprednisolone. These results suggest that vindesine is well tolerated and possesses some activity in patients with previously treated bronchogenic carcinoma.

Regional immunotherapy has a detrimental effect on the response to combined irradiation and chemotherapy in locally advanced non-small cell bronchogenic carcinoma

Twenty-one patients with stage III M0 non-oat cell bronchogenic carcinoma confined to the thorax were randomized to receive either intrapleural BCG (107 cfu, Tice strain) or intrapleural saline 3 weeks prior to beginning combined irradiation and chemotherapy. Radiation to the primary tumor and regional nodes was given at a dose of 3,000 rad in ten sessions and was followed in 7–14 days by CAMP chemotherapy (cyclophosphamide, adriamycin, methotrexate, and procarbazine) for a planned duration of 6 months. Isoniazid, 300 mg/day, was given to all patients for 3 months starting 1 week after intrapleural therapy. There were no significant differences in pretreatment prognostic factors or in response to radiation therapy. The patients receiving intrapleural BCG in addition to radiation and chemotherapy had a median survival of 18 weeks, significantly shorter than that for the patients receiving intrapleural saline (54 weeks, P=0.017).

Oral VP-16-213 in advanced bronchogenic carcinoma and toxic effects when combined with methotrexate.

Forty-six patients with histologically confirmed lung cancer received treatment with the cytotoxic drug VP-16-213 in a dose of 100 mg twice daily, given orally for five days. The overall objective response rate was 11 out of 46 (24%) or 11 of the 33 (33%) who survived to receive two cycles. The drug was effective in all histological types. Only one patient developed leucopenia. This demonstration of the safety of VP-16-213 and its effectiveness suggested that this drug might be used in combination chemotherapy. A series of pilot studies showed unexplained marrow toxicity when VP-16-123 combined with vincristine was given with either methotrexate of adriamycin.

PREVENTION OF ISOPHOSPHAMIDE-INDUCED UROTHELIAL TOXICITY WITH 2-MERCAPTOETHANE SULPHONATE SODIUM (MESNUM) IN PATIENTS WITH ADVANCED CARCINOMA

In 8 patients receiving intravenous isophosphamide 2 g/m2 at 2-week intervals for advanced bronchogenic carcinoma the protective effect of 2-mercaptoethane sulphonate sodium (mesnum) against isophosphamide-induced urothelial toxicity was tested in a single-blind crossover trial. With isophosphamide alone, 7 of the 8 patients developed either hæmaturia or symptoms of bladder irritation; when mesnum was given in addition, only 1 patient had microhæmaturia and frequency, and this was in association with a urinary-tract infection. 5 patients then received fifteen courses of isophosphamide in increasing doses of 4 to 8 g/m2 i.v. with mesnum. In contrast to previous experience with isophosphamide at this high dosage, frank hæmaturia was never seen, microhaematuria was seen after only three courses, and mild dysuria after only one course. Pharmacokinetic studies showed that mesnum did not interfere with the metabolism of isophosphamide or its active antitumour metabolite, isophosphoramide mustard. Mesnum therefore enhances the therapeutic ratio of isophosphamide and may thereby increase its clinical efficacy.

Combination chemotherapy of advanced non-oat cell carcinoma of the lung

A controlled clinical trial comparing combination chemotherapy was performed in 147 patients with advanced inoperable non-oat cell bronchogenic carcinoma. All patients were stratified according to cell type, performance status, and extent of disease. They were then randomized to one of two combination treatment regimens selected by cell type. In epidermoid carcinoma, the combination of CCNU, methotrexate, and adriamycin was found to be more effective than 5-fluorouracil and procarbazine both in terms of objective response rate (19% vs. 0%) and survival. Two patients (4%), one with extensive disease, are alive in complete remission for 424 + and 540 + days. In adenocarcinoma of the lung the combination of CCNU, cyclophosphamide, and methotrexate was more effective than 5-fluorouracil and adriamycin with objective response of 25% vs. 15% and improved median survival. Neither the combination of cyclophosphamide and adriamycin, or the combination of CCNU, procarbazine, and 5-fluorouracil had demonstrable activity in large cell carcinoma of the lung. Responders, both objective responders and stable responders, lived longer than patients with progressive disease among all histological types. The achievement of a complete remission appears to be necessary for significant survival prolongation in epidermoid carcinoma. Previous treatment did not influence response or survival. Extent of disease and performance status in addition to cell type influenced response and survival and patients with advanced lung cancer should be stratified according to these variables. Patients who were ≥50% bedridden rarely responded to treatment and had a significantly (p < .005) shorter survival.

CCNU-adriamycin therapy in bronchogenic carcinoma

Forty-eight patients with advanced bronchogenic carcinoma were treated with a combination of CCNU and Adriamycin. There was an overall objective response rate of 38%. This consisted of 1 of 12 (8%) patients with epidermoid carcinoma, 5 of 15 (33%) with adenocarcinoma, 2 of 5 (40%) with large cell undifferentiated carcinoma and 10 of 16 (63%) with small cell undifferentiated carcinoma. The overall median survival time (MST) from initiation of therapy was 28 weeks. The MST was 18 weeks for patients with epidermoid carcinoma, 30 weeks for those with adenocarcinoma, 39 weeks for those with large cell carcinoma, and 30+ weeks for those with small cell carcinoma. Objective tumor response was associated with prolonged survival. There were no drug related deaths and toxicity was minimal.

Bronchial artery infusion of mitomycin-C in advanced bronchogenic carcinoma.

Bronchial angiography was performed in 17 patients with advanced non-oat cell bronchogenic carcinoma. The patients were treated 1 to 5 times with infusions of 10 mg of mitomycin-C (MMC) into the tumor-feeding bronchial artery. All but 2 patients received in addition small doses of vincristine (intravenously) and bleomycin (intramuscularly) or only bleomycin to potentiate the effect of MMC. No major side effects occurred and the systemic toxicity was insignificant. An objective tumor reponse was encountered in 11/17 patients. Intraarterial chemotherapy is strictly local and therefore effective especially in patients with limited or locally advanced disease. In patients with more extensive disease an adjunctive therapy of a more regional or systemic modality must be given.

Treatment of advanced bronchogenic carcinoma with adriamycin, 5-fluorouracil and methotrexate

The combination of adriamycin, 5-fluorouracil and methotrexate with folinic acid reversal was used to treat patients with advanced bronchogenic carcinoma. Twenty-one of 30 patients showed an objective response. This combination appears to produce useful remissions in patients with non-squamous lung cancer.

Combination chemotherapy of advanced lung cancer.A randomized trial

A controlled clinical trial comparing two-drug and three-drug combination chemotherapy was performed in 206 patients with advanced bronchogenic carcinoma, comprised of 26.2% with epidermoid carcinoma, 30.1% with small cell anaplastic carcinoma, 27.2% with adenocarcinoma, and 15.6% with large cell carcinoma. Each drug combination consisted of agents with different modes of action and included a cell-cycle-stage nonsensitive and a cell-cycle-state-sensitive agent. The overall response rate was highest for small cell carcinoma (48.2%) and adenocarcinoma (23.6%); it was less than 10% in epidermoid and large cell carcinoma. Similarly, the overall median survival was twice as long for the first two cell types (7 months) as compared with that recorded for the other two cell types (3 1/2 months). The combination of 1 (2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was shown to be statistically superior to cyclophosphamide and methotrexate with regard to objective respones rate, duration of response, and median survival for adenocarcinoma. Responders lived significantly longer than nonresponders (254 versus 90 days for small cell anaplastic carcinoma patients and 244 versus 184 days for adenocarcinoma patients). No difference in survival or objective response rate was observed between the different treatments for the other two cell types of lung cancer.

Methyl-ccnu, alone and in combination with vincristine, or vincristine and methotrexate, in advanced bronchogenic carcinoma

Ninety-two patients with advanced bronchogenic carcinoma were prospectively randomized according to performance status, histology, and extent of disease to methyl-CCNU alone; methyl-CCNU and vincristine; or methyl-CCNU, vincristine, and methotrexate. Seventy-three patients were evaluable. Randomization to methyl-CCNU alone was discontinued when only three brief "static" responses were noted in 11 patients and the survival (p less than .01) and time on study (p less than .05) were noted to be significantly less than with the combination. Two of 32 patients treated with methyl-CCNU and vincristine, and two of 30 patients treated with methyl-CCNU, vincristine, and methotrexate had mixed responses with a median of 67.5 days. A static response was seen in eight of 32 and none of 30 patients, respectively. Minimal toxicity occurred in all regimens. Methyl-CCNU alone or in combination with vincristine or vincristine and methotrexate is of limited benefit in patients with lung cancer, although our data suggest (p = 0.15) that the addition of methotrexate increases time on study and survival in patients with extensive disease.