Page 9 - Read Online

Page 4 of 13 Abughanimeh et al. J Cancer Metastasis Treat 2020;6:50 I http://dx.doi.org/10.20517/2394-4722.2020.110

Hematologic toxicities were reported with lurbinectedin treatment. Grade 4 neutropenia was recorded in
25% of the patients, whereas grade 4 thrombocytopenia was recorded in 4%. None of the patients developed
grade 4 anemia, however 9% of them developed grade 3. Other non-hematologic toxicities included fatigue,
[16]
decreased appetite and different gastrointestinal symptoms .
Currently, a phase III clinical trial, the ATLANTIS study (NCT02566993) is being conducted to compare
the activity of lurbinectedin combined with doxorubicin, with either topotecan or CAV as second line
[10]
treatment for SCLC .

Irinotecan
Irinotecan is a water-soluble derivative of camptothecin that acts through inhibition of DNA
topotisomerase I, leading to antitumor effects . The use of irinotecan in SCLC has been established in
[19]
[19]
the last century. In 1990, a phase II study was conducted in Japan by Masuda et al. . This study enrolled
16 patients with refractory or relapsed SCLC. All patients received IV irinotecan 100 mg/m every week.
2
In this study, irinotecan led to an ORR of 47% (95%CI: 21.4%-71.9%). The median duration of response
was 58 days (28-156 days). These findings were supported by another study that was done in Japan
[20]
which demonstrated an ORR of 50% (95%CI: 25%-75%) . A newer study was conducted in Japan which
evaluated 30 patients with previously treated SCLC who received irinotecan 100 mg/m on days 1, 8, every
2
3 weeks. The study showed an ORR of 41.3% (95%CI: 25.5-59.3) and a disease control rate of 69%. The
[21]
same study showed a median PFS and OS of 4.1 months and 10.4 months, respectively .
The major toxicities associated with irinotecan treatment were hematologic, mostly leukopenia, followed by
[19]
nausea and pulmonary toxicity .
Taxanes
Paclitaxel was evaluated in multiple studies in patients with relapsed/refractory SCLC. A phase II trial was
2
[22]
performed by Smit et al. in Netherlands where patients received IV paclitaxel 175mg/m every 3 weeks.
Paclitaxel led to an ORR of 29% (95%CI: 12%-51%). Furthermore, it was associated with a median duration
of response of 108 days (64-243 days), median time to progression of 65 days (33-243days), and median
survival of 100 days (23-262 days).

[23]
Paclitaxel was assessed in another phase II trial that was conducted by Yamamoto et al. who studied
21 patients with refractory SCLC. The study showed that single agent IV paclitaxel at a dose of 80 mg/m 2
weekly had an ORR of 23.8% (95%CI: 5.59-42.03), with a median survival of 5.8 months. The most common
toxicity associated with paclitaxel was grade 3-4 neutropenia (66.6%), other reported side effects included
neuropathy, infections, and other gastrointestinal symptoms .
[23]
Docetaxel is another taxane that was studied in relapsed/refractory SCLC. In the mid-1990s, docetaxel was
[24]
studied in a phase II trial in patients with previously treated SCLC . The study showed that IV docetaxel
2
100 mg/m once every 3 weeks was associated with an ORR of 25%, with a median duration of response
ranging between 3.5 and 12.6 months. The main toxicities reported in this trial were neutropenia, alopecia,
[24]
and fatigue .
It is worth to mention that Cabazitaxel was also studied in the setting of relapsed SCLC, but a study
[25]
conducted by Evans et al. showed inferior PFS and OS when compared to topotecan.
Temozolomide
Temozolomide (TMZ) is an oral alkylating agent, which acts through production of O6 -alkyl-guanine
lesions on DNA. These lesions are removed by O6 -methylguanine-DNA methyltransferase (MGMT).