A phase II study of oxaliplatin and paclitaxel in patients with advanced non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin and paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The treatment regimen was given as defined in a phase I investigation in patients with previously treated ovarian cancer. It consisted of paclitaxel 175 mg/m(2) (1-h infusion) and oxaliplatin 130 mg/m(2) (2-h infusion) given every 21 days. Eligible patients had stage IIIB (pleural effusion)/IV NSCLC, measurable disease, no prior chemotherapy, Eastern Cooperative Oncology Group performance status 0-2, and adequate hematological, renal and hepatic function. RESULTS: A total of 38 patients were enrolled with the following characteristics: 29% male (n = 11); 71% female (n = 27); median age 64.5 years (range 37-78); performance status of 0-1 84% (n = 32); stage IIIB 8% (n = 3); stage IV 92% (n = 35). One hundred and eighty-one cycles were administered, with a median of four per patient (range one to 12). The overall objective response rate for all 38 patients was 34.2% [95% confidence interval (CI) 19.6% to 51.4%]. This response rate includes 13 patients who met criteria for a partial response. No complete responses were observed. Median overall survival time was 9.2 months (95% CI 6-12.4) and median progression-free survival time was 4.3 months (95% CI 2.1-6.5). The 1- and 2-year overall survival rates were 37% and 21%, respectively. Hematological toxicity included six patients with grade 4 neutropenia. Non-hematological toxicity consisted mainly of grades 1 and 2 neurosensory toxicity. Laryngodysesthesia was observed in two patients following oxaliplatin infusion. No grade 4 non-hematological toxicities were encountered. CONCLUSION: This regimen is well tolerated, and demonstrates activity in patients with advanced NSCLC.

A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study.

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.

Combination chemotherapy and radiation therapy for small cell carcinoma.

A three-drug combination of the chemotherapeutic agents cyclophosphamide, vincristine sulfate, and doxorubicin hydrochloride was given to 45 patients with small cell bronchogenic carcinoma. In addition, patients with limited disease received radiation therapy to the primary tumor. The complete response rate was 44%, with a median survival of 50 weeks. The partial response rate was 29%, with a median survival of 35 weeks. Patients who did not respond to therapy showed a median survival of only 12 weeks. Twenty percent of the patients had their first recurrence in the brain, and the median survival from the time of disease recurrence was ten weeks. Bone marrow metastasis was encountered in 24% of the patient population, but this did not adversely affect survival.

Survival with inoperable lung cancer: an integration of prognostic variables based on simple clinical criteria.

The objectives are to identify and integrate through regression analysis those fundamental clinical variables predicting survival of patients with inoperable lung cancer managed in a modern setting. Median survival time from first treatment in 129 patients with limited disease and 187 patients with extensive disease was 36 and 14 weeks, respectively. Within the proposed survival model for limited disease, weight loss was the major prognosticator followed by symptom status, supraclavicular metastases, and age. Within extensive disease, symptom status and age were dominant variables followed by weight loss and metastases to liver, opposite hemithorax, brain, and bone. Survival by cell type was similar within the limited and extensive disease groups. The data identify the essential factors which must be controlled or accounted for in studies analyzing survival as a dependent variable.

Large-dose bleomycin therapy and pulmonary toxicity. A possible role of prior radiotherapy.

Bleomycin sulfate pulmonary toxicity was encountered in nine of 101 patients receiving high-dose therapy for widespread testicular cancer. The pulmonary presentation was separable into two categories: (1) an early or minimal from with dyspnea on exertion, minimal roentgenographic findings, and normal arterial partial pressure of oxygen at rest and (2) a severe form, with prominent roentgenographic findings and hypoxemia at rest. All five patients with the severe form died, while the remaining four patients with the minimal presentation recovered. Prior thoracic radiotherapy appeared to predispose to bleomycin pulmonary toxicity, as this complication developed in five of 12 patients receiving prior chest radiotherapy vs four of 89 not receiving radiotherapy (p less than .001). The fatality rate of 5% with high-dose bleomycin therapy is acceptable in view of the 75% response rate and substantially improved survival achieved with bleomycin combination chemotherapy in metastatic testicular cancer.

Bleomycin (NSC-125066) followed by cyclophosphamide (NSC-26271), vincristine (NSC-67574), methotrexate (NSC-740), and 5-fllorouracil (NSC-19893) for non-oat cell bronchogenic carcinoma.

The in vivo observation that bleomycin may be used as a synchronizing agent provides the basis for testing 4 days of continuous bleomycin infusion followed by 5 days of intensive chemotherapy with cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil. Thirty-eight patients with extensive non-oat cell bronchogenic carcinoma (adenocarcinoma[17 patients], squamous cell carcinoma[14 patients], and poorly differentiated carcinoma [seven patients]) were registered for chemotherapy. There were 11 patients with 50% regression of all measurable lesions and four with improved but poorly measurable radiographic lesions, providing a crude response rate of 39% (15 of 38 patients). An overall survival median of 19 weeks compares favorably with Veterans' Administration Lung Cancer Study Group control data, but was not substantially better than our own historical controls (P = 0.15). The median survival for responders was 36 weeks compared to 16 weeks for historical controls (P = 0.001) and 12 weeks for nonresponders (P less than 0.001).

Chemotherapy for advanced Kaposi sarcoma.

Kaposi sarcoma is a rare disorder, usually controlled with conservative localized treatment. However, prognosis is serious for patients with aggressive cutaneous disease, and aminous for those with visceral involvement. Two cases of advanced Kaposi sarcoma are reviewed to illustrate a chemotherapeutic approach to patients with this disease. The first case represents a verified response of visceral Kaposi sarcoma to chemotherapy. The second provides an example of the control of aggressive dermatologic disease.

Intravenous hyperalimentation as an adjunct to cancer chemotherapy.

A 36 per cent response rate was obtained in fifty-eight nutritionally depleted patients with cancer who would otherwise have been denied adequate antitumor therapy because of the fear of complications from malnutrition and inanition. A positive correlation between the nutritional status of the patient and the chemotherapeutic tumor response was identified. Intravenous hyperalimentation can be a valuable adjunct to cancer chemotherapy by improving the nutritional status, increasing the total deliverable dose of anticancer agent per unit of time, and reducing the incidence and severity of the toxic gastrointestinal side effects without adversely stimulating malignant cell growth or producing septic complications.