Phase I study of escalating doses of oxaliplatin in combination with fixed dose gemcitabine in patients with non-small cell lung cancer.

PURPOSE: Oxaliplatin (OHP) is a new platinum antineoplastic, while gemcitabine (GEM) is one of the most active drugs against non-small cell carcinoma (NSCLC). The OHP/GEM combination is interesting because the drugs have different mechanisms of action and toxicity profiles. The primary endpoint of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OHP/GEM combination in non-small cell carcinoma of the lung. METHODS: Patients with relapsed NSCLC were treated with fixed dose i.v. GEM (1250 mg/m2) on days 1 and 8; followed on day 1 by i.v. OHP over 3 h, starting from 70 mg/m2 with 20 mg/m2 increments, up to 130 mg/m2. We enrolled 19 patients with eastern cooperative oncology group (ECOG) status 0/1=13/6; male/female=13/6. All had received first-line and four second-line chemotherapy. RESULTS: Four patients dropped out. At dose level 2, one patient died of pulmonary embolism; at level 3, two patients died of disease progression. One patient at level 3, refused to continue treatment after allergic reaction (high fever episode) during infusion of third cycle. Fifteen patients were evaluable for toxicity and response. According to a priori statistical considerations, three patients in each of the first three treatment levels and six in the last level were evaluable. No G3-4 toxicity was observed at levels 1 and 2. G3 neutropenia and anemia occurred in 8% of cycles at level 3. Six patients entered level 4 (OHP 130 mg/m2) with 22 courses delivered: G3-4 neutropenia occurred in 9%, G1-2 thrombocytopenia in 18%; other toxicities were mainly limited to G1-2 flu-like syndrome in about one third of patients and G1-2 nausea and vomiting in 5% of courses. There was no myelo-DLT at the highest dose level. There was no neurotoxicity at any level. Treatment was delayed in 12% and dose reduced in 26% of courses. There were 2/15 PR. CONCLUSIONS: MTD was not reached. OHP and GEM can probably be administered safely at 130 and 1250 mg/m2, respectively, as first-line therapy. The schedule is being used in a phase II trial.

Preoperative chemoradiation in patients with resectable rectal cancer: results on tumor response.

BACKGROUND: There is no consensus about the role of preoperative radiotherapy (RT) and chemotherapy (CT) in patients with resectable cancer of the distal rectum. This study analyzed the local clinical and pathologic response in patients receiving preoperative RT/CT for rectal cancer. METHODS: Thirty-two consecutive patients with a palpable adenocarcinoma of the rectum received preoperative RT (45 Gy in 25 fractions over 5 weeks) plus continuous chemotherapy with doxifluridine and leucovorin or 5-fluorouracil by continuous intravenous infusion during RT. Surgery was performed 8 weeks later. The Wilcoxon and chi(2) tests were used for data analysis. RESULTS: Twelve patients had mild gastrointestinal toxicity, only one of whom required interruption of therapy. The tumor shrank to 57.8% of its original size, and at the echoendoscopy (u) there was a 58.7% decrease of the maximum diameter (P <.001). Downstaging from uT3 and uT2 to

Ten-year survival with chemotherapy and radiotherapy in patients with squamous cell carcinoma of the esophagus.

BACKGROUND: The effects of multimodality treatment on the survival of patients with esophageal carcinoma are unclear. The authors performed a prospective, Phase II study to assess the long-term results of chemotherapy plus radiotherapy (RT) on patients with esophageal squamous cell carcinoma. METHODS: Of 106 consecutive patients who were recruited between 1985 and 1992, 101 patients were evaluable. Cisplatin (100 mg/m2 per day) on Day 1 and fluorouracil (1000 mg/m2 per day) on Days 1-4 were given for two cycles, with concomitant RT (30 grays [Gy] in 15 fractions) over 19 days. Patients with potentially resectable tumors were then assessed for curative surgery; the other patients received two more courses of chemotherapy and further RT (20 Gy in 10 fractions). RESULTS: Of 40 patients who were candidates for surgery, 32 patients underwent surgery, and 24 patients had complete resection; 8 patients (25%) had no residual tumor in the specimen, and 12 patients (37%) had microscopic foci only. Surgical mortality was high (22%). Of 61 nonsurgical patients, 37 patients (61%) achieved complete clinical remission, and 14 patients (23%) achieved partial remission. The median survival for the entire series was 15 months (range, 1-136 months). The overall survival rate was 22% at 5 years and 12% at 10 years. At 10 years, freedom from disease progression was similar in the two groups (24%), whereas the median survival (22 months vs. 12 months) and the overall survival rates (17% vs. 9%) were better in nonsurgical patients compared with surgical patients, respectively, probably in relation to high surgical mortality. The larynx was preserved in 28% of 32 patients with cervical disease sites, with a 10-year disease free survival rate of 31%. Three deaths were attributed to nonsurgical treatments. CONCLUSIONS: Careful multidisciplinary pretreatment evaluation can identify patients who are ineligible for surgery without compromising long-term results. For patients with inoperable disease, chemoradiotherapy can produce relatively good long-term results. The combined approach without surgery can permit laryngeal preservation in a useful fraction of patients.