Accurate laboratory predictions of the clinical response of patients with advanced ovarian cancer to treatment with cyclophosphamide, doxorubicin, and cisplatin

Stratton, Joan A.; Kucera, Paul R.; Rettenmaier, Mark A.; Dobashi, Kazuyoshi; Micha, John P.; Braly, Patricia S.; Berman, Michael L.; DiSaia, Philip J.

doi:10.1016/0090-8258(86)90081-8

Cited by 7 publications

(7 citation statements)

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“…Recent histologic observations in our laboratory 11 have indicated that the adaptation period could be as short as 2 weeks, reducing the entire process to 6 weeks. This relatively short period of 6 to 8 weeks makes the first generation xenografts, as distinct from transplantable tumor lines (13,15,24,36), suitable for clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…As an alternative approach, chemosensitivity of patients' cancers to various regimens can be evaluated using transplantable subcutaneous tumor lines developed from resected cancer specimens. Although such tumor lines are valuable for drug development and may lead to useful predictions (9)(10)(11)(12), the engraftment rate of s.c. implanted cancers is low (20-40%) and establishing transplantable tumor lines may take as long as 10 months (13)(14)(15)(16)(17), severely limiting the usefulness of this approach for personalized chemotherapy.…”

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confidence: 99%

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Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy

Dong

Guan

English

et al. 2010

Clinical Cancer Research

168

166

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Purpose: Current chemotherapeutic regimens have only modest benefit for non-small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients.Experimental Design: Pieces (1×3×3 mm 3 ) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area ≤50% of control, P < 0.05) were determined. Clinical outcomes of treated patients were acquired.Results: Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive.Conclusions: Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients. Clin Cancer Res; 16(5); 1442-51. ©2010 AACR.Lung cancer is the leading cause of cancer-related mortality worldwide (1). Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer deaths (2, 3). Chemotherapy has been shown to improve the survival of patients with advanced, inoperable NSCLCs or, as adjuvant therapy, to reduce the rate of relapse of patients following resection of early-stage cancers (2, 3). Generally, two-drug combinations of cytotoxic drugs such as gemcitabine, vinorelbine, and docetaxel with cisplatin or carboplatin are used. A recent meta-analysis study showed that platinum-based, adjuvant chemotherapy of patients with resected NSCLCs was associated with a 5% greater 5-year survival rate, revealing marginal effectiveness of current chemotherapeutic regimens (4). Moreover, only a portion of patients who receive first-line treatment can receive further chemotherapy because of rapid disease progression and intolerance to side effects. Additional chemotherapy is particularly limited for patients who have experienced severe toxic...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy

Dong

Guan

English

et al. 2010

Clinical Cancer Research

168

166

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“…Clinical response was taken as a complete or more than 50% regression verified at second look in our report and of at least 4 months' duration in the other three reports. The sensitivity and negative prospective value are extremely good, In addition, our laboratory has recently shown very good correlates for ovarian cancer (14). We have shown a 100% positive predictive accuracy for ovarian cancer patients whose tumors are sensitive to Cisplatin, Adriamycin, and Cytoxan; i.e., if the patient was sensitive to the administered drug(s), the SRC assay always predicted sensitivity.…”

Section: Results and Commentsmentioning

confidence: 83%

The murine subrenal capsule human tumor implant assay

Stratton

1987

Clinical Laboratory Analysis

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The murine subrenal capsule assay can be used to estimate the susceptibility of fresh human tumor explants to various antineoplastic agents. As a result, the assay has been proposed as a rapid and accurate preclinical laboratory evaluation to determine the sensitivity of human tumors to chemotherapeutic drugs and thereby to assist the direction of cancer patient treatment. The subrenal capsule assay is described in detail and the predictive accuracy of the assay in the clinical setting is discussed.

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“…The subrenal capsule assay (SRCA) (Bogden et al, 1981) correctly predicts the response to cytostatic chemotherapy in 63-85% of patients with previously untreated ovarian cancer (Bogden, 1985;Griffin et al, 1983;Maenpaa et al, 1985a,b;Stratton et al, 1984Stratton et al, , 1986Stratton et al, , 1988. The situation may differ in cases with recurrent cancer, when cell populations resistant to first-line chemotherapy have become selected out to form clinically detectable tumours (Maenpaa, 1985c).…”

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confidence: 99%

“…Four of the 11 patients (36%) whose further chemotherapy was strictly chosen based on the SRCA and seven of the 24 patients (29%) whose treatment was based on physician's choice survived at least 3 years. Our conclusion is that the SRCA is of limited value in the selection of second-line chemotherapy in recurrent ovarian cancer.The subrenal capsule assay (SRCA) (Bogden et al, 1981) correctly predicts the response to cytostatic chemotherapy in 63-85% of patients with previously untreated ovarian cancer (Bogden, 1985; Griffin et al, 1983; Maenpaa et al, 1985a,b;Stratton et al, 1984Stratton et al, , 1986 Stratton et al, , 1988 (Maenpaa, 1985c). There are some data to suggest that the SRCA could be useful in the selection of the second-line chemotherapy (Griffin et al, 1983;Maenpaa, 1985c), but so far no data exist on improved survival rates in patients whose second-line chemotherapy has been guided by the use of the SRCA.…”

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confidence: 99%

Subrenal capsule assay in selection of chemotherapy after operation for recurrent ovarian cancer

Venesmaa

Ylikorkala²

1991

Br J Cancer

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Summary Forty-six patients with recurrent ovarian cancer were reoperated, and cancer samples for the subrenal capsule assay (SRCA) were collected from 23 of them, whereas this test was not done in the remaining 23 control patients. The SRCA was evaluable in 22 cases (96%). Taken together, no significant difference appeared in the 3 years' survival figures between the groups: seven of 22 patients (32%) with the evaluable SRCA and six of 23 control patients (26%) were alive. However, a further analysis of the data revealed that the SRCA guided the selection of chemotherapy only in 15 patients, whereas tumour samples were resistant to all cytostatics tested in six cases and toxic side-effects limited the clinical application of the test results in the remaining one case. Four of the 11 patients (36%) whose further chemotherapy was strictly chosen based on the SRCA and seven of the 24 patients (29%) whose treatment was based on physician's choice survived at least 3 years. Our conclusion is that the SRCA is of limited value in the selection of second-line chemotherapy in recurrent ovarian cancer.The subrenal capsule assay (SRCA) (Bogden et al., 1981) correctly predicts the response to cytostatic chemotherapy in 63-85% of patients with previously untreated ovarian cancer (Bogden, 1985; Griffin et al., 1983; Maenpaa et al., 1985a,b;Stratton et al., 1984Stratton et al., , 1986 Stratton et al., , 1988 (Maenpaa, 1985c). There are some data to suggest that the SRCA could be useful in the selection of the second-line chemotherapy (Griffin et al., 1983;Maenpaa, 1985c), but so far no data exist on improved survival rates in patients whose second-line chemotherapy has been guided by the use of the SRCA. We therefore assessed the value of the SRCA in patients with recurrent ovarian cancer that were followed up to death or for a minimum of 3 years. Materials and methodsForty-six patients between 25 and 76 years of age with recurrent ovarian cancer were studied (Table I). The primary operation was radical in seven women, whereas tumours smaller than 2 cm of size remained in nine women and tumours larger than 2cm remained in 30 women. Serous cystadenocarcinoma was the most common type of cancer (22 women) followed by anaplastic cancer (11 women), miscellaneous cancer (nine women with mesonephric cancers and one with endometrioid cancer) and mucinous cystadenocarcinoma (three women) ( Table I). The cancer had spread to clinical stages III-IV in 37 women. All patients following surgery had been treated with 4-28 courses of various cytostatics, mostly with the combination of doxorubicin, cisplatin and cyclophosphamide (n = 34 patients). Thirty-five had responded favourably to the therapy, as assessed by the standard criteria (Miller et al., 1981), whereas in 11 women no response to therapy and/or progression of the disease was seen.These 46 patients entered our study with the approval of the local committee of ethics between 5-48 months after primary operation, when they came for a routine second-look (n = 32) and third-look (n ...

show abstract

Accurate laboratory predictions of the clinical response of patients with advanced ovarian cancer to treatment with cyclophosphamide, doxorubicin, and cisplatin

Cited by 7 publications

References 10 publications

Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy

Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy

The murine subrenal capsule human tumor implant assay

Subrenal capsule assay in selection of chemotherapy after operation for recurrent ovarian cancer

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