Developing drugs to decrease the toxicity of chemotherapy.
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Antineoplastic Agents↗
Biomedical subjects
P Cortazar
Publications and source records attributed to P Cortazar.
Review of the efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing for patients with cancer.
PURPOSE: The purpose of this study is to review the potential efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing (DST) compared with empiric regimens for patients with cancer. METHODS: MEDLINE and CANCERLIT were searched for articles published (in English) about prospective clinical trials in which patients were treated with chemotherapy that was selected with the use of in vitro DST. RESULTS: We identified 12 prospective studies that examined the benefit of chemotherapy selected by DST. Five hundred six patients (33%) were treated with chemotherapy that was selected with the use of in vitro DST. The mean response rate for patients treated with in vitro-selected therapy was 27% (range, 10% to 100%; n = 12 studies) compared with 18% (range, 0% to 100%; n = 7 studies) for patients treated with empiric therapy. Five studies (only one randomized) evaluated the impact of chemotherapy selected by in vitro DST on patient survival. Three studies showed that survival was 1 to 4 months longer for the 238 patients treated with empiric chemotherapy compared with that of the 65 patients treated with chemotherapy that was selected by in vitro testing. Two nonrandomized studies showed that survival was 4 or 19 months longer for 27 patients treated with chemotherapy selected by in vitro testing compared with that of 80 patients who were treated with empiric chemotherapy. CONCLUSION: Only one third of patients entered in prospective trials of in vitro DST were actually treated with an in vitro best regimen. The response rates seem to be better with in vitro selected chemotherapy regimens than with empiric regimens, but the impact on survival has not been adequately addressed.
Carcinoma, Small Cell↗
Second lung cancers in patients successfully treated for lung cancer.
The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.
Actuarial Analysis↗
Survival of patients with limited-stage small cell lung cancer treated with individualized chemotherapy selected by in vitro drug sensitivity testing.
Our purpose was to study the feasibility of determining individualized chemotherapy regimens by in vitro drug sensitivity testing (DST) for patients with limited-stage small cell lung cancer (SCLC) and to evaluate patient response and survival. Fifty-four previously untreated patients with limited-stage small cell cancer were studied. Fresh tumor specimens for DST were collected, when possible, from patients' biopsies before the start of treatment. The differential staining cytotoxicity assay was used to determine the in vitro sensitivity of the tumor cells to different drugs. From these results, an in vitro best regimen (IVBR), a three-drug combination of previously proven efficacy of seven active drugs in SCLC, was selected. Patients were initially treated with four cycles of etoposide/cisplatin and concurrent radiotherapy. This was followed by four cycles of either individualized chemotherapy regimens based on the results of DST or, when DST results were not available, four cycles of vincristine, doxorubicin, and cyclophosphamide. Eighteen patients (33%) underwent biopsy procedures that provided tissue specimens for DST. The biopsy specimens contained tumor cells in 16 of 18 patients. The median duration from diagnosis to start of treatment was 22 days (range, 4-58 days) for the 18 patients who underwent elective thoracic biopsies compared to 21 days (range, 2-74 days) for members of the group that did not (P2 = 0.58). Time from thoracic biopsy to initiation of chemotherapy was a median of 4 days (range, 2-22 days). DST was done in 10 patients, and IVBR was administered to 8 patients. The median actuarial survival of 8 patients treated with their IVBR was 38.5 months compared to 19 months for the 46 patients treated with empiric chemotherapy. Selection of individualized chemotherapy regimens is labor intensive but feasible in limited-stage SCLC. Treatment with an individualized IVBR in our patients was associated with prolonged patient survival; however, because of the nature of our study design, other factors could have affected the results.
Antineoplastic Agents↗