Docetaxel-induced lymphopenia in patients with solid tumors

Κotsakis, Athanasios; Sarra, E.; Peraki, Maria; Koukourakis, Michael I.; Apostolaki, Stella; Souglakos, John; Mavromanomakis, Emmanuel; Vlachonikolis, John; Georgoulias, Vassilis

doi:10.1002/1097-0142(20000915)89:6<1380::aid-cncr23>3.0.co;2-r

Cited by 47 publications

(33 citation statements)

References 19 publications

(18 reference statements)

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“…Their findings were consistent with a progressive decline in all T-lymphocyte subpopulations, namely CD3+, CD4+, CD8+, and CD56+ T or activated killer cells, but no or minimal effect on the CD20+ B-cell subpopulation. Very importantly, docetaxel caused a profound but reversible lymphopenia that was associated with an increased risk of non-neutropenic (very likely) opportunistic infections (Kotsakis et al, 2000). These findings might at first sight seem to contradict ours, however, the studies bear important differences in their design and the parameters evaluated.…”

Section: Clinicalcontrasting

confidence: 53%

“…A recent study reported by the University of Herakleion-Crete group evaluated various lymphocyte subpopulations before and after treatment with single-agent docetaxel, administered either weekly or 3-weekly, in 46 chemotherapy-naïve patients with a variety of solid tumours (Kotsakis et al, 2000). Their findings were consistent with a progressive decline in all T-lymphocyte subpopulations, namely CD3+, CD4+, CD8+, and CD56+ T or activated killer cells, but no or minimal effect on the CD20+ B-cell subpopulation.…”

Section: Clinicalmentioning

confidence: 65%

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Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes

Tsavaris¹,

Kosmas²,

Vadiaka³

et al. 2002

Br J Cancer

297

213

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Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1b, IFN-g, GM-CSF, IL-6, TNF-a, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by 3 H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-g levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-a and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-g levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P50.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-g, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-a levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-g, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-a. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel. Over the last decade, taxanes (namely paclitaxel and docetaxel) have emerged as effective antitumour agents in a variety of malignancies. Paclitaxel is a semi-synthetic taxane, isolated from the bark of the Pacific yew tree. Doxetaxel is a semi-synthetic taxane, derived from the needles of the European yew (Taxus Baccata). These compounds bind to tubulin, leading to microtubule stabilisation, mitotic arrest and, subsequently, cell death. Plasma clearance of paclitaxel exhibits non-linear kinetics, which results in ...

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Section: Clinicalcontrasting

confidence: 53%

Section: Clinicalmentioning

confidence: 65%

Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes

Tsavaris¹,

Kosmas²,

Vadiaka³

et al. 2002

Br J Cancer

297

213

View full text Add to dashboard Cite

show abstract

“…There are mixed reports in the literature on the effects of chemotherapy on NK cells. Although certain reports suggest that chemotherapy reduces the count and cytotoxicity of NK cells (12,19), another suggested an increase in NK cell cytotoxicity following chemotherapy (20). The present case report suggests that there is decrease in the in vitro expansion of NK cells with subsequent chemotherapy cycles.…”

Section: Discussionmentioning

confidence: 96%

“…The present case report suggests that there is decrease in the in vitro expansion of NK cells with subsequent chemotherapy cycles. Although earlier studies have discussed the effects of chemotherapy on either the count or the in vitro cytotoxicity of the NK cells (12,19,20), to the best of our knowledge the current report is the first to provide details on the in vitro expansion potential of the NK cells, which has clinical significance as these expanded cells were used for immunotherapy in the patient described herein. Tai et al (21) reported that surgical stress induces dysfunction of NK cells, impairing their cytotoxic ability, thereby promoting tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cell-based immunotherapy in stage IIIA inflammatory breast cancer with declining innate immunity following successive chemotherapies: A case report

Chidambaram¹,

Dedeepiya²,

Premkumar

et al. 2017

Molecular and Clinical Oncology

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Abstract. Cancer stem cells in breast cancer migrating to the bone marrow may cause future metastasis, particularly during periods of decreased immunity. Natural killer (NK) cells have a role in immune surveillance and are able to target cancer stem cells. The present study reported a case in which NK cell-based autologous immune enhancement therapy was used combined with conventional treatments in a patient with stage IIIA breast cancer, yielding >28 months of disease-free survival. However, there was a gradual decline in the in vitro expansion of NK cells with subsequent chemotherapeutic treatments. As this NK cell decline following chemotherapy may contribute to cancer cell immune evasion and future metastasis; modifying current cancer therapies in order to avoid potentially compromising the immune system may lead to improved treatment outcomes.

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“…Docetaxel chemotherapy or chemo -radiotherapy is associated with a dramatic reduction of Bcell, T-cell counts as well as natural killer counts (Koukourakis et al, 1998a(Koukourakis et al, , 1999aKotsakis et al, 2000). It may be, therefore, that the immunoreactive-cell count reduction induced by docetaxel accounts for the fever/rash symptomatology elimination.…”

Section: Clinicalmentioning

confidence: 99%

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

et al. 2002

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The substantial augmentation of the radiation sequelae during chemo -radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo -radiotherapy scheme with Stealth Ò liposomal doxorubicin (Caelyx Ò ) and Docetaxel (Taxotere Ò ) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere Ò was 20 mg m 72 week and of Caelyx Ò was 15 mg m 72 every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere Ò /Caelyx Ò was, thereafter, increased to 20/25 (five patients) and 30/25 mg m 72 (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The 'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere Ò / Caelyx Ò chemo -radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the 'in-field' toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer.

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Docetaxel-induced lymphopenia in patients with solid tumors

Cited by 47 publications

References 19 publications

Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes

Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes

Cell-based immunotherapy in stage IIIA inflammatory breast cancer with declining innate immunity following successive chemotherapies: A case report

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

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