Tumor response and progression-free survival as potential surrogate endpoints for overall survival in extensive stage small-cell lung cancer: findings on the basis of North Central Cancer Treatment Group trials.

Background: The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.

Methods: Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses.

Pretreatment quality of life is an independent prognostic factor for overall survival in patients with advanced stage non-small cell lung cancer.

Hypothesis: We conducted this pooled analysis to assess the prognostic value of pretreatment Quality of Life (QOL) assessments on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).

Methods: Four hundred twenty patients with advanced NSCLC (stages IIIB with pleural effusion and IV) from six North Central Cancer Treatment Group trials were included in this study. QOL assessments included the single-item Uniscale (355 patients), Lung Cancer Symptom Scale (217 patients), and Functional Assessment of Cancer Therapy-Lung (197 patients).

Impact of complete response to chemotherapy on overall survival in advanced colorectal cancer: results from Intergroup N9741.

Purpose: To evaluate clinical characteristics and survival outcomes among patients with locally advanced or metastatic colorectal cancer who achieve a complete response (CR) to systemic treatment either alone or with multimodality approach.

Patients And Methods: Data were collected retrospectively from CRC patients enrolled onto the phase III trial N9741, a National Cancer Institute-funded and Gastrointestinal Cancer Intergroup-sponsored study coordinated by the North Central Cancer Treatment Group. Patients were randomly assigned to combinations of oxaliplatin, fluorouracil (FU)/leucovorin (LV) and irinotecan.

Phase II trial of oxaliplatin/irinotecan/5-fluorouracil/leucovorin for metastatic colorectal cancer.

Background: Individually, oxaliplatin and irinotecan have substantial activity in metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin. A combination regimen using all 4 agents could potentially increase response rates in CRC.

Patients And Methods: A multicenter phase II trial of oxaliplatin 85 mg/m(2) on day 1, irinotecan 175 mg/m(2) on day 1, 5-fluorouracil 240 mg/m(2) by 90-minute infusion on days 2-5, and leucovorin 20 mg/m(2) on days 2-5 of a 21-day cycle was undertaken in patients with CRC through the North Central Cancer Treatment Group.

Impact of pretreatment factors on adverse events: a pooled analysis of North Central Cancer Treatment Group advanced stage non-small cell lung cancer trials.

Introduction: This pooled analysis was performed to examine the impact of pretreatment factors on severe (grade 3 or higher) adverse events (AE) in patients with advanced stage non-small cell lung cancer (NSCLC).

Methods: A pooled data set of 1053 participants from nine North Central Cancer Treatment Group clinical trials was used. Age, gender, performance status, tumor stage, body mass index, serum creatinine levels, hemoglobin levels, white blood cell counts, and platelet counts were evaluated univariately and multivariately using logistic regression.

Randomized clinical trial of high-dose levamisole combined with 5-fluorouracil and leucovorin as surgical adjuvant therapy for high-risk colon cancer.

Background: Levamisole combined with 5-fluorouracil (5-FU) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer. Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines. A clinical trial was designed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy.

A prognostic model for advanced stage nonsmall cell lung cancer. Pooled analysis of North Central Cancer Treatment Group trials.

Background: A pooled analysis was performed to examine the impact of pretreatment factors on overall survival (OS) and time to progression (TTP) in patients with advanced-stage nonsmall cell lung cancer (NSCLC) and to construct a prediction equation for OS using pretreatment factors.

Methods: A pooled data set of 1053 patients from 9 North Central Cancer Treatment Group trials was used. Age, gender, Eastern Cooperative Oncology Group performance status (PS), tumor stage (Stage IIIB vs.

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52.

Purpose: This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease.

Patients And Methods: Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause.

Two concurrent phase II trials of paclitaxel/carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252.

Purpose: The efficacy and tolerability of 2 different schedules of paclitaxel/carboplatin/trastuzumab for HER2-overexpressing metastatic breast cancer (MBC) were evaluated in this parallel multicenter phase II trial.

Patients And Methods: Patients received every-3-week therapy (n = 43) consisting of a 200 mg/m(2) dose of paclitaxel/carboplatin area under the curve (AUC) of 6 mg/mL per minute and trastuzumab (an initial 8 mg/kg dose and subsequent 6 mg/kg doses) administered every 21 days for 8 cycles or weekly therapy (n = 48) consisting of an 80-mg/m(2) dose of paclitaxel/carboplatin AUC of 2 mg/mL per minute for 3 of 4 weeks, with weekly trastuzumab (an initial 4-mg/kg dose and subsequent 2-mg/kg doses) administered every 4 weeks for 6 cycles. Trastuzumab was continued until disease progression or unacceptable toxicity.

Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial.

Background: Shark cartilage has been a popular complementary or alternative medicine intervention. The basis for this popularity is the claim that sharks rarely get cancer because of the high proportion of cartilage in the shark's body. However, early studies were equivocal.

Phase II trial of dolastatin-10 in patients with advanced breast cancer.

Purpose: Phase II multicenter cooperative group study investigated the efficacy and toxicity of the novel anti-microtubule agent dolastatin-10 in patients with advanced breast cancer.

Patient And Methods: Twenty-one patients with measurable metastatic breast cancer were treated with dolastatin-10 at a dose of 400 mcg/m2 by intravenous bolus once every 3 weeks. Patients must have received a total of 1 or 2 prior chemotherapy regimens and have an Eastern Cooperative Oncology Group performance status of 0-2.

Results of combined-modality therapy for limited-stage small cell lung carcinoma in the elderly.

Background: A Phase III trial was conducted by the North Central Cancer Treatment Group to determine whether chemotherapy (etoposide and cisplatin) plus either twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a better outcome for patients with limited-stage small cell lung carcinoma (LD-SCLC). No difference in survival was identified between the two arms. The current analysis examined the relation between age and outcome for patients treated during this trial.

Phase II study of gemcitabine plus cisplatin in patients with metastatic breast cancer: a North Central Cancer Treatment Group Trial.

Background: This 2-stage, phase II cooperative group trial examined the efficacy and toxicity of 1000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin weekly for 3 weeks and repeated every 28 days for patients with previously treated metastatic breast cancer.

Methods: Eligible patients had to have measurable metastatic disease. Progression on prior treatment with at least 1 chemotherapy program for metastatic disease and 1 prior anthracycline and/or taxane-containing regimen in either the metastatic or adjuvant setting was required.

Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy.

Purpose: To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.

Patients And Methods: This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.

Investigating the utility of serum cytokine measurements in a multi-institutional cancer anorexia/weight loss trial.

Background: Interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) have been implicated in the cancer anorexia/weight loss syndrome. However, previous smaller studies have yielded conflicting results as to whether circulating, serum concentrations of these cytokines are in fact elevated. As the translational component of a large multi-institutional trial, this study assessed the clinical value of serum concentrations of these cytokines in patients with this syndrome.

Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both.

Purpose: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.

Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer.

Purpose: This Phase III study was performed to determine whether twice-daily (b.i.d.

Oral vinorelbine for the treatment of metastatic non-small cell lung cancer in elderly patients: a phase II trial of efficacy and toxicity.

Purpose: Before now oral vinorelbine has not yet been tested in a cohort of elderly, advanced non-small cell lung cancer patients, even though the intravenous form of this drug provides a reasonable therapeutic option for this group. This trial was conducted to determine the tumor response rate and toxicity profile of oral vinorelbine in advanced non-small cell lung cancer patients > or = 65 years of age.

Patient And Methods: Fifty-eight evaluable patients > or = 65 years of age with advanced non-small cell lung cancer were enrolled.

Phase II study of oral etoposide and intravenous paclitaxel in extensive-stage small cell lung cancer.

Background: This study evaluated the activity and tolerance for the combination of oral etoposide and paclitaxel as first-line therapy for patients with extensive SCLC.

Methods: A total of 57 patients were enrolled in this study. A cycle of chemotherapy consisted of oral etoposide administered as 50 mg BID on days 1 through 10 and paclitaxel administered as 150 mg/m(2) IV (3 h infusion) along with the first dose of etoposide on day 10.

Prognostic value of proliferation, apoptosis, defective DNA mismatch repair, and p53 overexpression in patients with resected Dukes' B2 or C colon cancer: a North Central Cancer Treatment Group Study.

Purpose: Molecular studies of colon cancer have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting prognosis. This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas.

Patients And Methods: Tumor tissue from 366 patients (75% Dukes' C, 25% Dukes' B2) from four randomized North Central Cancer Treatment Group phase III surgical adjuvant trials were used.

A phase II study of the dolastatin 15 analogue LU 103793 in the treatment of advanced non-small-cell lung cancer.

A phase II study of the dolastatin 15 analog LU 103793 was conducted by the North Central Cancer Treatment Group in patients with advanced non-small-cell lung cancer (SCLC). Previously untreated patients received this agent at a dosage of 2.5 mg/m2 as a 5-minute intravenous infusion for 5 consecutive days every 3 weeks.

Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking.

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy.

Participants And Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention).

Brief physician-initiated quit-smoking strategies for clinical oncology settings: a trial coordinated by the Eastern Cooperative Oncology Group.

Purpose: Although tobacco use by cancer patients increases the risk of relapse, diminishes treatment efficacy, and worsens quality of life, about one third of patients who smoked before their diagnosis continue to smoke. Because patients have regular contact with oncologists, the efficacy of a physician-based smoking cessation treatment was evaluated.

Methods: Cancer patients (n = 432) were randomly assigned to either usual care or a National Institutes of Health (NIH) physician-based smoking intervention.

Randomized, placebo-controlled, phase III surgical adjuvant clinical trial of megestrol acetate (Megace) in selected patients with malignant melanoma.

A randomized, double-blind, placebo-controlled phase III clinical trial was performed to assess megestrol acetate (Megace) as a postsurgical adjuvant therapy for patients with locally advanced malignant melanoma. Patients whose tumors were greater than 1.7 mm thick and had no regional lymph node involvement and patients with regional lymph node involvement were randomized to receive either 160 mg twice per day oral suspension of megestrol acetate or placebo.

Early detection of toxicity and adjustment of ongoing clinical trials: the history and performance of the North Central Cancer Treatment Group's real-time toxicity monitoring program.

Prospective clinical trials are the gold standard for evidence-based methodology used to support changes in the practice of medicine. Clinical researchers, regulatory agencies, payers, and the public embrace the conduct of phase I, II, and III clinical trials as integral to improving patient care. The National Cancer Institute (NCI) funds a number of cooperative oncology groups to conduct such clinical trials in the United States.