Transient therapy-related surge in serum tumor biomarkers: Characterizing behavior and postulating its biologic role

Mundle, Suneel; Marathe, Anuj; Chelladurai, Mohanathasan

doi:10.1016/j.critrevonc.2012.09.006

Cited by 14 publications

(15 citation statements)

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“…Interestingly, such a "flare" response has been observed with CEA among 11% of patients with mCRC during the initial cycles of chemotherapy, which has been associated with better prognosis. [32][33][34] In conclusion, both intermittent and concomitant schedules of erlotinib were active and well tolerated when administered together with a modified XELOX regimen, with a (nonsignificantly) higher response rate favoring the INT arm. This study provides further evidence that erlotinib has meaningful activity in mCRC regardless of KRAS mutation status when combined with chemotherapy.…”

Section: Discussionmentioning

confidence: 77%

“…The number of responders were 13 (of 16 patients, 81.2%) in the “flare” group and 24 (of 42 patients, 57.1%) in patients without the “flare” response, but this difference was insignificant. Interestingly, such a “flare” response has been observed with CEA among 11% of patients with mCRC during the initial cycles of chemotherapy, which has been associated with better prognosis …”

Section: Discussionmentioning

confidence: 99%

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Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer

B.Y.

Chan

et al. 2013

Cancer

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BACKGROUND: This study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer. METHODS: A total of 60 untreated patients were randomized to a "continuous" (CON; erlotinib 100 mg daily) or an "intermittent" (INT; erlotinib 150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21) schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin) regimen. Serum levels of AREG and TGFa were determined serially. RESULTS: Baseline characteristics were similar between the 2 arms. Of the 58 patients evaluated for response, there was a nonsignificant trend toward a slightly higher overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a median follow-up of 2.8 years, the median overall survival was 18.8 months (95% confidence interval 5 11.3-22.9 months) and 20.7 months (95% confidence interval 5 12.5-31 months, P 5.19) for the CON and INT arm, respectively. KRAS mutation did not predict drug response. The 2 arms did not differ significantly in toxicity. Baseline serum TGFa was an independent predictor of progression-free survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of treatment were associated with shorter progression-free survival and overall survival, respectively. CONCLUSIONS: The intermittent erlotinib schedule was associated with a higher response rate, although this is not statistically significant. Serum TGFa and AREG levels have prognostic significance in erlotinib-treated patients with colorectal cancer, and further studies are warranted. Cancer 2013;119:4145-53. V C 2013 American Cancer Society.KEYWORDS: erlotinib, oxaliplatin, capecitabine, amphiregulin, transforming growth factor alpha. INTRODUCTIONThe development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) in the treatment of metastatic colorectal cancer (mCRC) has taken a new turn with the recent reports on the DREAM 1 and the DUX studies, 2 which showed that erlotinib may play a role when combined with either bevacizumab 1 or cetuximab 2 in the palliative treatment of mCRC. Studies in preclinical models of CRC have demonstrated an additive to synergistic effect on growth inhibition when an EGFR TKI is combined with chemotherapy. 3 Furthermore, this inhibitory effect could be scheduledependent in CRC cells, such that synergism could be better observed when chemotherapy was administered before the EGFR TKI rather than concomitantly, whereas antagonism maybe observed if EGFR TKI is given before the cytotoxic agent. 4,5 Drug scheduling may also be important when combining EGFR TKI and cytotoxic agents, as shown in lung cancer models, where an intermittent schedule of EGFR TKI was more effective in controlling tumor growth than a continuous schedule. 6 Despite the number of clinical reports on the activity of combining EGFR TKI and chemotherapy in mCRC, none of them have evaluated the ...

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer

B.Y.

Chan

et al. 2013

Cancer

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“…Persistently rising values above baseline on three separate occasions suggest progressive disease (PD) even in the absence of corroborating radiographs [2]. Caution is, however, necessary when interpreting a rising CEA level during the first 4-6 weeks of a new therapy, since spurious early rises of CEA may occur especially after oxaliplatin-based chemotherapy [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Can carcinoembryonic antigen replace computed tomography in response evaluation of metastatic colorectal cancer?

et al. 2018

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“…While tumor markers have been used to monitor the effects of systemic therapy for specific tumor types, their general use in oncology practice is hampered by difficulties in interpreting changes [63]. One exception is prostate specific antigen (PSA), which is useful for monitoring treatment effects for prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer

Amin

Bathe

2016

BMC Cancer

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BackgroundThe rapidly expanding arsenal of chemotherapeutic agents approved in the past 5 years represents significant progress in the field. However, this poses a challenge for oncologists to choose which drug or combination of drugs is best for any individual. Because only a fraction of patients respond to any drug, efforts have been made to devise strategies to personalize care. The majority of efforts have involved development of predictive biomarkers. While there are notable successes, there are no predictive biomarkers for most drugs. Moreover, predictive biomarkers enrich the cohort of individuals likely to benefit; they do not guarantee benefit.Main textThere is a need to devise alternate strategies to tailor cancer care. One alternative approach is to enhance the current adaptive approach, which involves administration of a drug and cessation of treatment once progression is documented. This currently involves radiographic tests for the most part, which are expensive, inconvenient and imperfect in their ability to categorize patients who are and are not benefiting from treatment. A biomarker approach to categorizing response may have advantages.ConclusionHerein, we discuss the state of the art on treatment response assessment. While the most mature technologies for response assessment involve radiographic tests such as CT and PET, reports are emerging on biomarkers used to monitor therapeutic efficacy. Potentially, response biomarkers represent a less expensive and more convenient means of monitoring therapy, although an ideal response biomarker has not yet been described. A framework for future response biomarker discovery is described.

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Transient therapy-related surge in serum tumor biomarkers: Characterizing behavior and postulating its biologic role

Cited by 14 publications

References 39 publications

Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer

Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer

Can carcinoembryonic antigen replace computed tomography in response evaluation of metastatic colorectal cancer?

Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer

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