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Biomedical subjects

Mark R Green

Publications and source records attributed to Mark R Green.

At least 19 recordsLinked to original sources
PubMed2006

Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935.

BACKGROUND AND OBJECTIVES: CALGB 8935 was a phase II protocol for mediastinoscopically staged IIIA (N2) non-small cell lung cancer. Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes. METHODS: Failure-free survival was calculated from a landmark 3 months after resection to account for heterogeneity in adjuvant therapy. RESULTS: Nine of 42 (21%) resected patients had no residual N2 disease. This subset of 9 had a median failure-free interval of 47.8 months from landmark, whereas the 33 patients (79%) with persistent N2 disease had a median failure-free survival of 8.2 months from landmark (P=0.01). Although 21/42 (50%) had an incomplete resection (positive highest resected node and/or margin), completeness of resection did not influence failure-free survival. There were 3 distant and no local recurrences among the N2 negative group, and 12 local recurrences among patients with residual N2 disease (P=0.041). CONCLUSIONS: These data suggest: (1) persistent N2 disease following induction chemotherapy is unfavorable; (2) patients downstaged to N2 negative may benefit from surgical resection; however, (3) 33% of N2 negative patients suffered disease relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The cancer and leukemia group B respiratory committee.

The Cancer and Leukemia Group B Respiratory Committee has a 30-year track record of clinical investigation in patients with small-cell lung cancer and non-small-cell lung cancer (NSCLC) and mesothelioma. The most widely recognized contributions of the Committee include the early confirmation of the role of concurrent chemoradiotherapy in LD-SCLC, the effect of combination chemotherapy followed by radiation in stage III NSCLC, the introduction of third-generation agents into concurrent chemoradiation for stage III disease, the prospective demonstration of the benefit of treating older (70 years old) and poorer performance status (performance status = 2) patients with first-line combinations for stage IV disease, and the development of the "Herndon prognostic index" to normalize patient characteristics and outcomes in sequential phase II trials of new agents in patients with mesothelioma. Many other contributions have also emerged from the Committee's clinical trials and correlative science programs. We look forward to making additional critical contributions during future decades of Cancer and Leukemia Group B Respiratory Committee research.

Antineoplastic Agents↗
PubMed2006

How do U.S. medical oncologists learn and apply new clinical trials information from press releases in nonmedical media? A case study based on ECOG 4599.

BACKGROUND: Practicing oncologists are expected to easily assimilate large amounts of rapidly evolving clinical data. We hypothesized that U.S. oncologists rapidly familiarize themselves with new, practice-relevant, phase III clinical trial data. We tested this hypothesis in relation to the release of phase III data from the Eastern Cooperative Oncology Group 4599 trial on the role of bevacizumab in advanced non-small cell lung cancer (NSCLC). METHODS: We queried approximately 310 medical oncologists concerning their awareness of the bevacizumab data within 1 and 3 weeks after the data release or immediately after the 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO). RESULTS: Prior to the ASCO meeting, 57% and 56% of the oncologists in the two research meetings, respectively, indicated "awareness" of the data release. Less than 25% selected an accurate descriptor of the released information from a short list of plausible options. After the ASCO meeting, the figures were 88% and 34%. Over 50% said they plan to use bevacizumab in NSCLC treatment as soon as reimbursement is secure. Eighty-two percent said they plan to use it in second- or third-line treatment; 56% said they plan to use it during second-line chemotherapy despite progression during first-line use. A large majority intend to use bevacizumab in dosages, tumor types, drug combinations, and/or patients not specifically supported by phase III data. CONCLUSION: Release of clinically relevant phase III data through electronic and print media is a poor vehicle for informing U.S. medical oncologists. For a commercially available agent, this can have important implications for potential use in untested and potentially unsafe clinical settings. Effective educational strategies for dealing with the new paradigm of "instant" release of clinical data need to be developed.

Antibodies, Monoclonal↗
PubMed2005

Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

PURPOSE: Among patients with small-cell lung carcinoma, African Americans have lower survival rates than non-African Americans. We investigated whether the disparity in survival would persist when patients were treated with similar therapies (ie, phase II/III Cancer and Leukemia Group B [CALGB] trials). PATIENTS AND METHODS: We assessed 995 patients (928 non-African American and 67 African American) receiving chemotherapy in CALGB studies for extensive-stage small-cell lung cancer (ES-SCLC). Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. The Cox proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two sided. RESULTS: The unadjusted survival distribution of African American patients was not significantly different from that of non-African American patients; median survival was 11.5 months (95% CI, 9.4 to 13.4 months) for African American patients versus 9.9 months (95% CI, 9.6 to 10.3 months) for non-African American patients. Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the outcome for African American patients. Survival was similar even though African American patients were more likely to have a poorer performance status, present with significant weight loss, and be Medicaid recipients (20% v 6%), which is an indicator of lower socioeconomic status. CONCLUSION: African American patients tended to present with prognostic features associated with a worse survival. However, when offered equivalent therapy, the outcome for African American patients was the same as that observed for non-African American patients.

Adult↗
PubMed2005

Concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer.

Over the last two decades, several approaches to multimodality therapy have been investigated in patients with advanced unresectable non-small cell lung cancer. These include induction chemotherapy and concurrent chemoradiotherapy. Both approaches have been shown to be superior to radiation therapy alone. However, in several randomized trials, concomitant chemoradiotherapy was shown to be superior to the induction chemotherapy approach. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, either as induction or as consolidation chemotherapy, might further improve survival rates. Recently, the Cancer and Leukemia Group B reported on a randomized phase III trial directly evaluating the addition of two cycles of carboplatin and paclitaxel to concurrent chemoradiotherapy. In this study, induction chemotherapy failed to further improve survival rates of concurrent chemoradiotherapy. A previously conducted randomized phase II study also suggested no benefit from the addition of induction chemotherapy to concomitant chemoradiotherapy. Favorable phase II data have been published supporting the use of consolidation chemotherapy. However, to date, no large randomized study evaluating a possible benefit from consolidation chemotherapy has been completed. In addition to evaluating optimal sequencing strategies of combined modality therapy, current investigations are also focusing on the integration of novel agents, including chemotherapeutic and targeted therapies. Currently ongoing trials involving novel approaches are reviewed here.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732.

PURPOSE: To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. PATIENTS AND METHODS: Eligible patients (N=587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). RESULTS: Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. CONCLUSION: PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.

Adult↗
PubMed2005

Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma. EXPERIMENTAL DESIGN: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity. RESULTS: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression. CONCLUSIONS: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.

Adult↗
PubMed2005

Irinotecan for malignant mesothelioma A phase II trial by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B (CALGB) conducted a multi-center phase II trial to evaluate the activity of irinotecan in malignant mesothelioma (CALGB protocol 9733). PATIENTS AND METHODS: Twenty-eight patients accrued between January 1998 and January 1999 received irinotecan 125 mg/m2 by intravenous infusion over 90 min weekly for 4 weeks, every 6 weeks. Eligibility included a performance status of 0-2 by CALGB criteria, and no prior chemotherapy. Twenty-five patients had pleural mesothelioma; two patients had peritoneal mesothelioma, and one patient had pericardial mesothelioma. Sixty-one percent of patients had epithelial histology. RESULTS: There were no complete or partial responders. Thirty-three percent of patients had stable disease and 52% were shown to have progressive disease at the first reassessment. One patient was not evaluable for response. Median survival from study entry was 9.3 months (95% CI 4.5-13.2 months); 1-year survival was estimated at 46% (95% CI 28-65%). Toxicity was moderately severe. Grade 3 or 4 toxicities included neutropenia in 28% of patients, lymphopenia in 43%, and diarrhea in 18%. Three patients died of treatment-related toxicities. All three experienced grade 4 diarrhea, two also had neutropenic sepsis. CONCLUSION: Single-agent irinotecan in this dose and schedule has considerable toxicity in patients with malignant mesothelioma and has no anti-tumor activity. The relatively long median survival seen in this study principally reflects the prognostic features of the accrued patients.

Adult↗
PubMed2005

Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004).

PURPOSE: This Phase II trial was designed to determine the response rate, survival, failure-free survival, and toxicity of second-line therapy with karenitecin in patients with relapsed or refractory non-small cell lung cancer (NSCLC). METHODS: Eligibility criteria included: only one prior chemotherapy program, measurable disease, performance status 0-1, adequate hematologic, renal, and hepatic function. Cases were stratified as relapsed or refractory. RESULTS: Fifty-five patients were accrued and 52 were eligible of whom 28 had relapsed and 24 had refractory disease. Overall patient characteristics were: median age 63 years (range, 45-79 years), 52% males, 63% performance status 1, 50% adenocarcinoma, 21% squamous, 15% large cell, and 12% undifferentiated NSCLC. In both strata, one patient each (4%) had a partial response and 12 patients each (43% for relapsed, 50% for refractory) had stable disease. Median survival was 10.4 months (95% CI, 8.5-17.0) for relapsed NSCLC and 6.0 months (95% CI, 3.7-9.7) for refractory NSCLC. One-year survival was 36% (95% CI, 14-58%) and 21% (95% CI, 5-37%) for relapsed and refractory NSCLC, respectively. Frequent toxicities were neutropenia (grade 3/4 in 15/15%) and thrombocytopenia (grade 3/4 in 17/8%). No patient had lethal toxicity. CONCLUSION: Second-line treatment with karenitecin was tolerable with reversible bone marrow suppression as the major toxicity. The partial response rates, median survival times, and 1-year survival rates in the relapsed and refractory subgroups are comparable to overall second-line outcomes for other agents considered active in this clinical setting.

Aged↗
PubMed2005

Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from CALGB 9761, a prospective trial.

PURPOSE: A major problem with the staging system for non-small cell lung cancer (NSCLC) is clinical underestimation of the extent of disease. Many patients with clinical stage 1 disease do not retain that designation following surgical resection. Herein, we present data from Cancer and Leukemia Group B (CALGB) protocol 9761 evaluating the correspondence between clinical and pathologic analysis in early stage NSCLC. METHODS: Five hundred and two patients with suspected or biopsy-proven NSCLC classified as clinical stage 1 (T1-2, N0) by computed tomography (CT) scan or cervical mediastinoscopy were prospectively enrolled in CALGB 9761. The purpose of CALGB 9761 was to prospectively evaluate molecular markers of micrometastatic disease in stage 1 NSCLC. Enrollment occurred at 11 selected institutions within the CALGB. Patients with clinically suspected resectable early stage lung cancer were eligible for enrollment if they had no evidence of mediastinal or hilar adenopathy on CT scan or if they had CT evidence of potential N2 or N3 disease (lymph node > or =1.0 cm) but with negative mediastinoscopy. No prior chemotherapy or radiotherapy was permitted. RESULTS: Of the 502 patients felt to have clinical stage 1 NSCLC enrolled in CALGB 9761, 489 underwent resection with complete surgical staging and routine histopathologic analysis. From these 489 patients, only 422 (86.3%) turned out to have pathologically documented NSCLC. Of these 422 patients, 302 (71.6%) had pathologic stage 1 disease (173 stage 1A and 129 stage 1B). Despite clinical assessment of stage 1 disease, 59 (14%) patients had pathologic stage 2 disease, 57 (13.5%) had stage 3 disease, and four (0.9%) patients had stage 4 disease. Of the patients undergoing resection for clinical stage 1 NSCLC, 65 patients did not have NSCLC (44 had benign disease and 21 had malignancies other than NSCLC) and two additional patients had dual synchronous primary NSCLC tumors and were not eligible for the study. Overall, only 61.7% (302 of 489) of patients with suspected stage 1 NSCLC disease retained that stage and diagnosis after complete surgical staging, while 38.3% had an inaccurate pre-operative clinical stage or diagnosis. CONCLUSIONS: The results from this prospective trial demonstrate the poor predictive value of current clinical staging techniques in early stage NSCLC. These findings will serve as a benchmark for comparison of future clinical imaging modalities and other tests evaluating early stage NSCLC.

Biopsy↗
PubMed2005

Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730).

PURPOSE: We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer. PATIENTS AND METHODS: A total of 561 eligible patients were randomly assigned to receive paclitaxel alone or in combination with carboplatin. RESULTS: The response rate was 17% in the paclitaxel arm and 30% in the carboplatin-paclitaxel arm (P < .0001). Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm (P = .0002). Median survival times were 6.7 months (95% CI, 5.8 to 7.8) and 8.8 months (95% CI, 8.0 to 9.9), and 1-year survival rates were 32% (95% CI, 27% to 38%), and 37% (95% CI, 32% to 43%), respectively. The overall survival distributions were not statistically different: hazard ratio = 0.91 (95% CI, 0.77 to 1.17; P = .25). Hematological toxicity and nausea were more frequent in the combination arm, but febrile neutropenia and toxic deaths were equally low in both arms. There was no significant survival difference in elderly patients. Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy (P = .019). CONCLUSION: Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy, but there was no statistically significant difference in the primary end point of overall survival. The results in elderly patients were similar to younger patients. Performance status 2 patients had a superior outcome when treated with combination chemotherapy.

Adult↗
PubMed2005

Patterns of surgical care of lung cancer patients.

BACKGROUND: This survey was performed to determine the patterns of surgical care provided patients with non-small cell lung carcinoma (NSCLC). METHODS: In 2001, the American College of Surgeons carried out a patient care survey of 729 hospitals to retrieve information of NSCLC patients' history, evaluation, pathology, and surgical treatment. RESULTS: Inclusion criteria were met by 40,090 patients: of whom 11,668 (29.1%) were treated surgically; 74.2% alone and 25.8% as part of multimodality therapy. Of these patients, 59.5% were in stage I, 17.5% in stage II, 17.0% in stage III, and 6.0% in stage IV. Surgery patient demographics were the following: 55% male and 45% female; 46.8% 70 years or older; and 76.3% had significant comorbidities. Tumor characteristics: squamous 28%, adenocarcinoma 37.6%, other 34.4%. Staging: in addition to radiologic examinations, preoperative mediastinoscopy was performed in 27.1% of operated patients with node biopsy in only 46.6% of these procedures. OPERATIONS: wedge resection 15.6%, lobectomy 70.8%, pneumonectomy 13.6%. Surgical margins were positive in 7.8%, but only 65.2% had frozen section analysis. Perioperative mortality was 5.2%, but was 4.0% in nontransfused patients and 12.7% in transfused patients and was 3.2% in high-volume (more than 90 operations per year) versus 4.8% in low-volume hospitals (p < 0.001). CONCLUSIONS: (1) Patients being operated for NSCLC are elderly with significant comorbid conditions. (2) More patients than previously are female and have adenocarcinoma. (3) Mediastinoscopy is infrequently performed and lymph nodes are biopsied in less than 50% of them. (4) Lobectomy is the most common operation, and positive surgical margins are too frequent. (5) Operative mortality is reasonable but transfusion is a marker for increased risk and outcomes are superior in high-volume hospitals. (6) Hospitals with higher volume had fewer perioperative deaths.

Adolescent↗
PubMed2005

A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235).

Based on both clinical and laboratory data that suggested that tamoxifen (TAM) enhanced the effectiveness of cisplatin (DDP)-based chemotherapy regimens, the Cancer and Leukemia Group B (CALGB) designed and initiated a prospective, randomized phase III trial to test the efficacy of the addition of high-dose TAM to a standard chemoradiation regimen of DDP and etoposide (VP-16) in patients with limited-stage small cell lung cancer (LS-SCLC). Between August 6, 1993, and January 15, 1999, 319 patients with LSSCLC were accrued to CALGB 9235. Patients were randomized to receive chemotherapy with or without high-dose TAM. Treatment on the non-TAM containing arm (arm 1) included DDP (80 mg/m2 intravenously day 1 only) and VP-16 (80 mg/m2 intravenously days 1-3) given every 3 weeks for a total of 5 cycles. Patients treated on arm 2 received the identical chemotherapy regimen as described here with the addition of high-dose TAM (80 mg orally twice per day), which was given for 5 days each cycle starting 1 day before the DDP. Thoracic radiation (XRT) given at 200 cGy 5 days per week to a total dose of 50 Gy began on day 1 of cycle 4 of chemotherapy and overlapped with cycle 5. Prophylactic cranial irradiation was offered to all patients who achieved a complete response or near-complete response. A total of 307 patients are evaluable for response. After the completion of the chemoradiation portion of the treatment, the overall response rate (ORR) was 88% for 154 patients treated without tamoxifen and 84% for 153 patients treated with tamoxifen with complete response (CR) rates of 49% and 50%, respectively. The median failure-free survivals of 12.3 months and 10.5 months and the overall survivals of 20.6 months and 18.4 months, respectively, were not statistically significant between the 2 arms. Toxicity was similar with and without tamoxifen. This phase III trial failed to demonstrate a positive effect on either the response or survival for the addition of TAM to standard etoposide-cisplatin-radiation management for patients with LS-SCLC. However, these data continue to support a positive effect of chemoradiation in the treatment of patients with LS-SCLC.

Aged↗
PubMed2005

Induction paclitaxel/carboplatin followed by concurrent chemoradiation therapy for unresectable stage III non-small-cell lung cancer: a limited-access study--CALGB 9534.

BACKGROUND: This phase II cooperative group study of patients with unresectable stage III non-small-cell lung cancer was designed to treat patients with induction chemotherapy with paclitaxel and carboplatin (PC) followed by concurrent chemotherapy with the same chemotherapy plus thoracic irradiation to 66 Gy. PATIENTS AND METHODS: All enrolled patients were scheduled to receive 2 cycles of induction PC at conventional doses. All nonprogressing patients were subsequently treated with concurrent chemoradiation, including 7 weekly doses of PC and once-daily thoracic irradiation. The eligibility criteria allowed treatment of an expanded population of patients, unrestricted by previous weight loss. RESULTS: Despite the fact that 22% of patients had experienced > 5% weight loss in the preceding 6 months, 23 of the 40 eligible patients (58%) responded to the overall regimen. A 3-year failure-free survival rate of 15% and a 3-year overall survival rate of 27% were achieved. The 3-year overall survival rate is consistent with landmark cooperative group results for the combined modality treatment of a more highly selected patient population. CONCLUSION: The feasibility of this therapeutic approach in a cooperative group setting and inclusive of patients who were representative of the general population of stage III lung cancer patients was established.

Adult↗
PubMed2004

Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.

PURPOSE: This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety. RESULTS: In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar. CONCLUSION: IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.

Aged↗
PubMed2004

A phase I study of sequential administration of escalating doses of intravenous paclitaxel, oral topotecan, and fixed-dose oral etoposide in patients with solid tumors.

BACKGROUND: Based on preclinical findings and on the clinical antitumor efficacy of sequential paclitaxel/topotecan and topotecan/etoposide, the authors sought to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) associated with a sequential combination of paclitaxel, topotecan, and etoposide in patients with solid tumors. METHODS: The MTDs were determined through standard dose escalation in cohorts of three patients. Patients with refractory solid tumors and performance status < or = 2 were treated with intravenous paclitaxel 50-110 mg/m(2) (Day 1), oral topotecan 0.5-2.0 mg/m(2) (Days 2-4), and oral etoposide 160 mg/m(2) (Days 5-7) during every 21-day cycle. For dose-limiting neutropenia, granulocyte-colony-stimulating factor (G-CSF) was administered on Day 8 in subsequent cohorts. Blood samples were obtained before treatment during Cycle 1 (Days 1, 2, and 5) for topoisomerase I assessment. RESULTS: Twenty-eight patients received a combined total of 129 cycles. The MTDs were paclitaxel 80 mg/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) without G-CSF. In minimally pretreated patients, G-CSF allowed paclitaxel dose escalation to 110 mg/m(2). Three patients (11%) had radiologic partial responses, and 4 patients (14%) had stable disease. Day 2 topoisomerase I levels increased by 2-15 times relative to baseline levels in 7 of 14 patients analyzed (50%). CONCLUSIONS: The novel sequential combination that was evaluated generally was well tolerated and active in patients with refractory solid tumors. Based on hematologic DLTs, the authors recommend further evaluation of paclitaxel 110 mg/m(2), topotecan 1.5 mg/m(2), and etoposide 160 mg/m(2) with G-CSF support in minimally pretreated patients.

Administration, Oral↗
PubMed2004

70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808.

PURPOSE: To prospectively evaluate the feasibility of delivering 70 Gy once-daily thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of limited-stage small-cell lung cancer (L-SCLC). MATERIALS AND METHODS: Eligible patients received two cycles of induction paclitaxel (175 mg/m(2) on Day 1) and topotecan (1 mg/m(2) on Days 1-5) with granulocyte colony stimulating factor support, followed by three cycles of carboplatin (area under the curve = 5 on Day 1) and etoposide (100 mg/m(2) on Days 1-3). TRT (70 Gy, 2 Gy/fx/7 weeks) was initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial irradiation was offered to patients achieving a complete response or good partial response. RESULTS: Ninety percent of patients (57 of 63) proceeded to protocol TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4 toxicities affecting more than 10% of patients, during or after TRT, were dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all therapy was 92% and the median overall survival is 22.4 months (95% confidence interval 16.1, infinity ). Twenty-eight patients remain alive with a median follow-up of 24.7 months. CONCLUSION: 70 Gy once-daily TRT can be delivered safely in the cooperative group setting for patients with L-SCLC. Initial efficacy data are encouraging. The hypothesis that high-dose once-daily TRT results in comparable or improved survival compared with twice-daily accelerated TRT warrants testing in a Phase III trial.

Adult↗