\title{irinotecan / s-1 toxicity dataset}
\description{12 studies investigating the occurrence of dose limiting toxicities (dlts) at different doses of a combination therapy of irinotecan and s-1.}
\bold{dose}   \tab \code{numeric}   \tab dose (\eqn{\mathrm{mg} / \mathrm{m}^2}) \cr
\bold{events} \tab \code{integer}   \tab number of dlts \cr
\bold{total}  \tab \code{integer}   \tab number of patients exposed \cr
a combination therapy of irinotecan (a topoisomerase 1 inhibitor) and s-1 (a combination of three pharmacological compounds, namely, tegafur, gimeracil, and oteracil potassium) was tested in advanced colorectal and gastric cancer. this dataset contains data from twelve studies investigating this therapy in a japanese population; it contains the doses investigated, the numbers of patients treated, and the number of dose-limiting toxicities (dlts) observed. in general, each study investigated several doses according to some dose-escalation scheme.
ursino, m., \enc{röver}{roever}, c., zohar,  s., & friede t. (2021). random-effects meta-analysis of phase i dose-finding studies using stochastic process priors. \emph{the annals of applied statistics}, \bold{15}(1), 174--193. \verb{https://doi.org/10.1214/20-aoas1390}
\enc{röver}{roever}, c., ursino, m., friede, t., & zohar, s. (2022). a straighforward meta-analysis approach for oncology phase i dose-finding studies. \emph{statistics in medicine}, \bold{41}(20), 3915--3940. \verb{https://doi.org/10.1002/sim.9484}
european medicines agency (ema) (2021). onivyde pegylated liposomal (irinotecan hydrochloride trihydrate) epar summary. \verb{https://www.ema.europa.eu/en/medicines/human/epar/onivyde-pegylated-liposomal}
european medicines agency (ema) (2022). teysuno (tegafur/gimeracil/oteracil) epar summary. \verb{https://www.ema.europa.eu/en/medicines/human/epar/teysuno}
yamada, y., yasui, h., goto, a., \emph{et al.} (2003). phase i study of irinotecan and s-1 combination therapy in patients with metastatic gastric cancer. \emph{international journal of clinical oncology}, \bold{8}(6), 374--380. \verb{https://doi.org/10.1007/s10147-003-0359-z}
takiuchi, h., narahara, h., tsujinaka, t., \emph{et al.} (2005). phase i study of s-1 combined with irinotecan (cpt-11) in patients with advanced gastric cancer (ogsg 0002). \emph{japanese journal of clinical oncology}, \bold{35}(9), 520--525. \verb{https://doi.org/10.1093/jjco/hyi148}
inokuchi, m., yamashita, t., yamada, h., \emph{et al.} (2006). phase i/ii study of s-1 combined with irinotecan for metastatic advanced gastric cancer. \emph{british journal of cancer}, \bold{94}(8), 11130. \verb{https://doi.org/10.1038/sj.bjc.6603072}
nakafusa, y., tanaka, m., ohtsuka, t., \emph{et al.} (2008). phase i/ii study of combination therapy with s-1 and cpt-11 for metastatic colorectal cancer. \emph{molecular medicine reports}, \bold{1}(6), 925--930. \verb{https://doi.org/10.3892/mmr_00000051}
ishimoto, o., ishida, t., honda, y., munakata, m., & sugawara, s. (2009). phase i study of daily s-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer. \emph{international journal of clinical oncology}, \bold{14}(1), 43--47. \verb{https://doi.org/10.1007/s10147-008-0796-9}
ogata, y., sasatomi, t., akagi, y., ishibashi, n., mori, s., & shirouzu, k. (2009). dosage escalation study of s-1 and irinotecan in metronomic chemotherapy against advanced colorectal cancer. \emph{the kurume medical journal}, \bold{56}(1+2), 1--7. \verb{https://doi.org/10.2739/kurumemedj.56.1}
shiozawa, m., sugano, n., tsuchida, k., morinaga, s., akaike, m., & sugimasa, y. (2009). a phase i study of combination therapy with s-1 and irinotecan (cpt-11) in patients with advanced colorectal cancer. \emph{journal of cancer research and clinical oncology}, \bold{135}(3), 365--370. \verb{https://doi.org/10.1007/s00432-008-0480-5}
yoshioka, t., kato, s., gamoh, m., \emph{et al.} (2009). phase i/ii study of sequential therapy with irinotecan and s-1 for metastatic colorectal cancer. \emph{british journal of cancer}, \bold{101}, 1972--1977. \verb{https://doi.org/10.1038/sj.bjc.6605432}
komatsu, y., yuki, s., fuse, n., \emph{et al.} (2010). phase 1/2 clinical study of irinotecan and oral s-1 (iris) in patients with advanced gastric cancer. \emph{advances in therapy}, \bold{27}(7), 483--492. \verb{https://doi.org/10.1007/s12325-010-0037-2}
kusaba, h., esaki, t., futami, k., \emph{et al.} (2010). phase i/ii study of a 3-week cycle of irinotecan and s-1 in patients with advanced colorectal cancer. \emph{cancer science}, \bold{101}(12), 2591--2595. \verb{https://doi.org/10.1111/j.1349-7006.2010.01728.x}
yoda, s., soejima, k., yasuda, h., \emph{et al.} (2011). a phase i study of s-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients. \emph{cancer chemotherapy and pharmacology}, \bold{67}(3), 717--722. \verb{https://doi.org/10.1007/s00280-010-1539-y}
goya, h., kuraishi, h., koyama, s., \emph{et al.} (2012). phase i/ii study of s-1 combined with biweekly irinotecan chemotherapy in previously treated advanced non-small cell lung cancer. \emph{cancer chemotherapy and pharmacology}, \bold{70}(5), 691--697. \verb{https://doi.org/10.1007/s00280-012-1957-0}
xlab="dose (mg / m²)", ylab="proportion",
main="dat.roever2022 (irinotecan / s-1 data)")
idx <- (dat.roever2022$study == studylab[i])