Is better drug availability in secondary neoplasms responsible for better response to chemotherapy?

Donelli, M.G.; Colombo, Tina; Dagnino, G.; Madonna, Mary Beth; Garattini, Silvio

doi:10.1016/0014-2964(81)90037-2

Cited by 11 publications

(3 citation statements)

References 11 publications

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“…As previously described [10], the intramuscular Lewis lung carcinoma shows a growth pattern very similar to its pulmonary metastases, but this pattern was differently modified by AM therapy ( fig. 1).…”

Section: Resultssupporting

confidence: 51%

Influence of Adriamycin on Growth Kinetics of Lewis Lung Carcinoma and Its Lung Metastases

et al. 1983

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Using a Gompertzian pharmacodynamic model, we have studied the changes induced by graded doses of adriamycin (AM) on the growth of intramuscular Lewis lung carcinoma (3LL) and its lung metastases in C57B1/6 mice. An interpretation of the drug’s effects on free growth of the tumor cells is given in the Appendix. Unlike other tumors (1–6), in which AM treatment induces no long-term change in growth parameters, in the 3LL model after an initial phase of inhibited growth following treatment with AM, the theoretically attainable plateau value is lowered. This is dose dependent for the primary tumor and even more so for metastases. In order to investigate whether the drug effect was irreversible or whether the host’s weakened condition was a factor in the altered growth conditions, the tumor and its metastases were removed from AM-treated mice and transplanted in healthy animals in which its growth was then observed over time. For transplants of the primary intramuscular tumor no differences could be seen between treated and nontreated mice, but for the metastases the growth was markedly slowed. However, after a ‘lag’ period, the tumors arising from metastases returned to a growth pattern whose kinetic parameters, analyzed statistically, were not different from controls.

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Section: Resultssupporting

confidence: 51%

Influence of Adriamycin on Growth Kinetics of Lewis Lung Carcinoma and Its Lung Metastases

et al. 1983

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“…With doxorubicin, however, there was strong abrogation of the sunitinib-augmented metastasis, but only a moderate effect on the primary tumor. Cytotoxic drugs have different activity on the primary tumor and metastatic sites and this was particularly evident for doxorubicin (40,41). However, it is very possible that the outcome of chemotherapy is influenced by the tumor microenvironment, such as vascular cells that can be susceptible to angiogenesis inhibitors in combination with chemotherapy (42).…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Rovida

Castiglioni

Decio

et al. 2013

Molecular Cancer Therapeutics

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The development of resistance and progressive disease after treatment with angiogenesis inhibitors is becoming a controversial issue. We investigated the experimental conditions that cause multireceptor tyrosine kinase inhibitors (RTKI) to augment metastasis and whether opportune combinations with chemotherapy could counteract this effect. The renal Renca-luc tumor was transplanted orthotopically in the kidney of Balb/c mice, which then were or were not nephrectomized. The Lewis Lung carcinoma (LLC) was transplanted in the tibial muscle of C57/Bl6 mice. Treatment with the RTKI sunitinib started at different stages of tumor progression, mimicking neoadjuvant or adjuvant settings. Combination studies with paclitaxel, doxorubicin, cisplatin, gemcitabine, and topotecan were done on the LLC model, using opportune regimens. In a neoadjuvant setting, sunitinib inhibited Renca-luc tumor growth, prolonging survival despite an increase in lung metastasis; treatment after primary tumor surgery (adjuvant setting) or on established metastasis prolonged survival and decreased metastasis. Sunitinib increased lung metastasis from mice bearing early-stage LLC, but did not affect established metastases (no acceleration) from advanced tumors. Combinations with doxorubicin, topotecan, gemcitabine, but not cisplatin and paclitaxel, counteracted the increase in metastasis from LLC, partly reflecting their antitumor activity. Histology analysis after sunitinib confirmed tumor vascular changes and increased hypoxia. Topotecan at suboptimal daily doses reduced sunitinib-related metastasis, reducing tumor hypoxia. Tyrosine kinase inhibitors, as sunitinib, can have adverse malignant effects mainly in the neoadjuvant setting. The addition of chemotherapy might influence metastasis, depending on each drug mechanism of action and its regimen of administration.

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“…This preferential accumulation of anticancer agents in metastasis is not limited to adriamycin but has been shown for other drugs too, such as daunomycin, etoposide, teniposide, hexamethylmelamine [20,21]. In general the preferential accumulation of anticancer drugs in metastasis compared to primary tumor appears to be more marked for drugs that distribute rapidly from blood to tissue.…”

Section: S Garattinimentioning

confidence: 89%

Review perspectives in the treatment of cancer metastasis

Garattini

1987

Clin Exp Metast

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IntroductionStudies of cancer dissemination and metastasis have recently received new impetus after a period of scant interest as a research topic. Yet dissemination and metastasis represent the essence of malignancy and no therapeutic intervention can be envisaged that does not affect the ability of the cells to migrate to other organs. Even the hope of finding a 'magic bullet' that kills all the cancer cells in the primary tumor would not always achieve the desired result because several types of human cancers disseminate quite early, even before they become visible and detectable for diagnosis.It is beyond the aim of this article to summarize the multiple facets of cancer dissemination which involve a large number of cellular functions including migration, interaction with other cells, transport in blood and lymph, arrest and extravasation in target organs, and interaction with the coagulation system. This introductory lecture~', rather than attempting an overview of the problem, discusses selected aspects of cancer metastasis, with particular reference to the research work carried out in these laboratories.

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Is better drug availability in secondary neoplasms responsible for better response to chemotherapy?

Cited by 11 publications

References 11 publications

Influence of Adriamycin on Growth Kinetics of Lewis Lung Carcinoma and Its Lung Metastases

Influence of Adriamycin on Growth Kinetics of Lewis Lung Carcinoma and Its Lung Metastases

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Review perspectives in the treatment of cancer metastasis

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