Adjuvant chemotherapy in non-small cell lung cancer.

Adjuvant chemotherapy is considered a standard of care for many malignancies, the most well known being breast and colon cancer. Unfortunately, less than a third of patients with non-small cell lung cancer (NSCLC) present with resectable disease and despite resection outcomes are often poor with a median 5-year survival of 40-50%. Modern chemotherapy for NSCLC provides both a survival advantage and an improvement in quality of life in the palliative setting. Several large studies using modern platinum-based regimens have been presented since the 1995 meta-analysis. This demonstrated a nonsignificant benefit for older platinum-based regiments. These studies have consistently shown a survival benefit across all stages of resection with acceptable toxicity. The absolute magnitude of benefit is consistent with that achieved in other malignancies where adjuvant chemotherapy is offered as a standard of care.

The management of PS2 patients with advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in the Western world. Patients with impaired performance status (PS2 or greater) have both worse prognosis and toxicity from treatment in general. The median survival of PS2 patients with advanced NSCLC is 4-5 months in comparison with the 8-9 months expected for those with good performance status (PS0-1). PS2 represents 30%-40% of all patients with advanced NSCLC, and their management remains controversial. In general, they have been excluded from most clinical trials. The emphasis on treatment should be on maintenance and improvement of quality of life with treatment strategies that provide rapid clinical improvement.

Symptomatic responses to neoadjuvant chemotherapy for carcinoma of the oesophagus and oesophagogastric junction: are they worth measuring?

AIMS: Neoadjuvant chemotherapy is used to downstage locally advanced oesophagogastric cancer. This study assessed whether changes in dysphagia and weight correlated with radiological and pathological assessment of response and surgical decision-making. MATERIALS AND METHODS: All patients with locally advanced carcinoma of the lower oesophagus or oesophagogastric junction treated with neoadjuvant ECF (epirubicin, cisplatin, and 5-fluorouracil) chemotherapy from January 2000 to January 2003 were included in this study. Patients were considered to be operable depending upon their chemotherapy response. Weight and swallowing were assessed before and after chemotherapy. Statistical analysis was carried out using ANOVA, unpaired t test and Fisher's exact test. RESULTS: Seventy-eight patients (male-female ratio: 6.8: 1; median age: 62.2 years; range: 44.1-78.0 years) underwent a median of three cycles (range: 1-7) of neoadjuvant ECF chemotherapy. Forty patients (51%) gained weight, and swallowing improved in 53 patients (68%). Radiological changes (based on computed tomography) were assessed according to WHO criteria: complete response (5%), partial response (27%), stable disease (46%) and progressive disease (15%). Patients whose swallowing improved gained significantly more weight (P < 0.0001). Swallowing (P = 0.0009) was significantly improved in radiological responders but not weight (P = 0.06); when radiological non-responders were separated into stable and progressive disease, patients with progressive disease were identified as failing to gain weight (P = 0.005). Both swallowing (P < 0.0001) and weight gain (P < 0.0001) were better in patients undergoing surgery. The use of changes of weight (P = 0.42) and swallowing (P = 0.61) failed to separate pathological responders from nonresponders in the subset of patients undergoing surgery. CONCLUSIONS: Weight gain and improved swallowing are good but not absolute indicators of radiological response to chemotherapy and patient selection for surgery. However, changes in these variables are not sufficiently sensitive to identify pathological responders from non-responders.

Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with suboptimally debulked, advanced epithelial ovarian cancer. A phase II trial of sequential doublets. The GO-First Study.

OBJECTIVES: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity. We studied the efficacy and toxicity of this combination in patients with advanced ovarian cancer when given prior to carboplatin and paclitaxel. METHODS: Chemonaive patients with epithelial ovarian cancer and measurable disease were eligible for the study. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days (GO) for 4 cycles. This was followed by carboplatin AUC = 6 and paclitaxel 175 mg/m2 on day 1 every 21 days (CP) for 4 cycles. RESULTS: Twenty patients, median age 62 years (range 39-78), FIGO stages III (16) and IV (4) received treatment. The response rate (RR) after 4 cycles of GO was 80% (95%CI 61-99%) (4 complete responses (CR), 12 partial responses (PR)). Interval debulking surgery was performed in 7 patients (35%). After CP chemotherapy, RR increased to 85% (95%CI 68-100%) (CR = 13, PR = 4). Median time to progression was 14.5 months. Estimated median overall survival was 31.5 months. Toxicities of GO were mild; grade 3/4 nausea in 3 patients (15%) and vomiting in 2 patients (10%), grade 3/4 neutropenia in 5 patients (25%). Grade 2/3 peripheral neuropathy occurred in 5 patients (25%). After sequential administration of CP, grade 2/3 neuropathy occurred in 13 patients (72%). CONCLUSION: The sequential doublet regimen of GO followed by CP resulted in unacceptable neurotoxicity and is not recommended for further study; however, the doublet gemcitabine and oxaliplatin has significant activity in the first line treatment of patients with ovarian cancer.

Neoadjuvant chemotherapy for locally advanced carcinoma of the lower oesophagus and oesophago-gastric junction.

AIMS: To evaluate a single unit's experience with neoadjuvant chemotherapy for treating locally advanced non-metastatic initially resectable and unresectable oesophago-gastric cancer. METHODS: The medical records of all patients with either locally advanced carcinoma of the lower oesophagus or cardia treated with neoadjuvant chemotherapy between August 1999 and January 2003 were reviewed. RESULTS: Sixty-four patients with initially resectable tumours (T2-3 or N+) and 38 patients with initially unresectable tumours (T4 or M1a) received neoadjuvant chemotherapy (83% combination Epirubicin, Cisplatin and 5-Fluorouracil). Symptomatic grade III/IV toxicity was observed in 33% of patients. Chemotherapy was not completed in 20 patients because of death (5.9%) and inadequate tumour response/toxicity (13.7%). Forty-three patients (67.3%) with initially resectable tumours and 19 patients (50%) with initially unresectable tumours underwent surgery. CONCLUSIONS: Chemotherapy in this study was associated with appreciable toxicity. Patients with initially unresectable locally advanced disease can be downstaged with neoadjuvant chemotherapy.

Management of the elderly patient with advanced non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most lethal of the common solid malignancies. It is predominantly a disease of the elderly with the median age at diagnosis 68 years. Unfortunately, the majority of patients present with advanced disease whereby palliation is the primary aim of treatment. The elderly have a long history of undertreatment and non-inclusion in clinical trials with regard to cancer. Elderly-specific studies demonstrate that chemotherapy provides both a survival and quality-of-life benefit in advanced NSCLC. Increasing emphasis is placed on the objective assessment of fitness for chemotherapy and the integration of molecularly targeted agents into treatment paradigms.