Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity

Cree, Ian A.; Kurbacher, Christian M.; Untch, Michael; Sutherland, Lesley; Hunter, Elizabeth M.; Subedi, A. M. C.; James, Elizabeth A.; Dewar, John; Preece, P. E.; Andreotti, Peter E.; Bruckner, Howard W.

doi:10.1097/00001813-199608000-00002

Cited by 72 publications

(51 citation statements)

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“…This fact is also supported by other reports, 14,15 which demonstrated that the ATP-based assay was sensitive enough to test cell viability with very small specimens. A short test turnaround time in our assay resulted from cutting the incubation time down to 48 hours, as reported in other studies, 25,26 with rising drug concentrations. These technical advantages would allow our ATP-CRA to be easily applied in clinical trials and perhaps eventually in clinical practice.…”

Section: Discussionmentioning

confidence: 77%

Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer

Moon

Choi

Kim³

et al. 2007

Cancer

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BACKGROUND.The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP‐CRA) and clinical outcomes after ATP‐CRA‐guided platinum‐based chemotherapy for unresectable nonsmall‐cell lung cancer (NSCLC).METHODS.The authors performed an in vitro chemosensitivity test, ATP‐CRA, to evaluate the chemosensitivities of anticancer drugs such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine for chemonaive, unresectable NSCLC. The cell death rate was determined by measuring the intracellular ATP levels of drug‐exposed cells compared with untreated controls. A sensitive drug was defined as a drug producing 30% or more reduction in ATP compared with untreated controls. Assay‐guided platinum‐based 2‐drug chemotherapy was given to patients with pathologically confirmed NSCLC.RESULTS.Thirty‐four patients were enrolled. Thirty tumor specimens were obtained by bronchoscopic biopsies and 4 obtained surgically. The median age was 61 years and 27 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. The response rate was 43.8%. At a median follow‐up period of 16.9 months, the median progression‐free and overall survivals were 3.6 and 11.2 months, respectively. Patients were dichotomized into the platinum‐sensitive (S; 20 patients) and resistant (R; 14 patients) groups. The positive/negative predictive values were 61.1% and 78.6% with a predictive accuracy of 68.8%. Although without significant differences in pretreatment parameters, the S‐group showed better clinical response (P = .036), longer progression‐free survival (P = .060), and longer overall survival (P = .025).CONCLUSIONS.Despite using bronchoscopic biopsied specimens, ATP‐CRA and clinical outcomes correlated well after assay‐guided platinum‐based 2‐drug chemotherapy for unresectable NSCLC. There was a favorable response and survival in the platinum‐sensitive vs resistant groups. Cancer 2007. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 77%

Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer

Moon

Choi

Kim³

et al. 2007

Cancer

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“…In the present study, we excluded potential prognostic effects as well as interference with other systemic therapies by using a wellestablished in vitro assay (ATP-TCA) for primary tumour cells (Andreotti et al, 1995;Cree et al, 1996;Kurbacher et al, 1996;Hengstler et al, 1999b;Konecny et al, 2000) in a consecutive series of 53 primary breast cancers. The ATP-TCA has been shown to allow a prediction of clinical results.…”

Section: Discussionmentioning

confidence: 99%

“…The ATP-TCA has been shown to allow a prediction of clinical results. The ATP-TCA-directed chemotherapy has improved clinical outcome in several studies (Andreotti et al, 1995;Cree et al, 1996;Kurbacher et al, 1996;Konecny et al, 2000). It should be considered that our ATP assay measures chemosensitivity on a cellular level, which is only one of several parameters relevant for clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer

Bremer¹,

Hasenclever

Victor

et al. 2007

Br J Cancer

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Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85 -27.2 mg ml À1 paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT -PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P ¼ 0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P ¼ 0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P ¼ 0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols. Taxanes like paclitaxel play an important role in the adjuvant treatment of breast cancer (Henderson et al, 2003). The efficacy of paclitaxel containing treatment can be further improved by dose dense protocols in which the chemotherapy is administered every 2 weeks with G-CSF support. Arguably, sequential protocols in which paclitaxel is administered not only dose dense, but also dose intensified, might prove to be even more efficient. Despite the well-documented antitumour efficacy of paclitaxel, many tumours exhibit intrinsic resistance to paclitaxel. These patients will obviously not profit from addition of paclitaxel to an anthracycline-based adjuvant chemotherapy. Identifying these patients could not only spare them an ineffective treatment, but gives the opportunity to establish a more efficient protocol for this particular subgroup of paclitaxel-resistant patients. In the adjuvant setting, Henderson et al (2003) have shown that especially patients whose tumours were oestrogen receptor (ER) negative derived most of the benefit from adding paclitaxel to an anthracyclin-based regimen. However, it is not entirely clear whether in this setting the prognostic impact of the hormone receptor status and the effect of adjuvant treatment with tamoxifen might thus offset a potential predictive effect of the hormone receptor status for paclitaxel chemosensitivity.

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“…In a recent study of the chemosensitivity of uveal melanoma ex vivo (Myatt et al, 1997), we used an ATP-based luminescence assay (Hunter et al, 1993;Andreotti et al, 1995;Cree et al, 1996;Kurbacher et al, 1998) to determine the sensitivity of primary uveal melanoma to a variety of chemotherapeutic agents. We observed variable sensitivity to treosulfan, cytosine arabinoside, paclitaxel and doxorubicin and showed enhancement of the response to treosulfan by cytosine arabinoside (Myatt et al, 1997).…”

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confidence: 99%

Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

et al. 1999

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Summary Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress.

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Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity

Cited by 72 publications

References 0 publications

Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer

Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer

Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

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