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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Both topotecan and irinotecan are derivatives from the Camptotheca acuminata tree. As with the nonpregnant population, the most pronounced maternal toxicity associated with topotecan is myelosuppression. To date, there have been no human studies evaluating the teratogenicity of this compound, and unlike most other antineoplastic agents, there are no reports of any pregnant patients receiving this drug. However, animal studies have been concerning. At levels equivalent to human doses, topotecan has been associated with reduced fetal body weight, fetal demise, fetal resorption, and brain, skull, and vertebrae malformations. Most commonly, malformations of the eyes were noted, including microphthalmia, anophthalmia, retinal defects, and ectopic orbits. Granted, most fetal effects are seen by early pregnancy exposure, in the absence of any human data, it is not recommended that topotecan be used at any time during pregnancy.
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
One useful feature of topotecan is that it can be given orally as well as by intravenous infusion. In the UK it is used by both delivery routes for the treatment of metastatic ovarian cancer, recurrent carcinoma of the cervix (after radiotherapy, and for patients with Stage IVB disease in combination with cisplatin), and by intravenous infusion for relapsed small-cell lung cancer when re-treatment with the first-line regimen is inappropriate.
An Introduction to the Ethnopharmacology of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Shandesh Bhattarai, Christiane Mendes Feitosa, Mahendra Rai
The first agents to advance into clinical use were the isolation of the vinca alkaloids, vinblastine, and vincristine from Catharanthus roseus, for the treatment of cancer followed by the discovery of paclitaxel from Taxus brevifolia (Kinghorn 1994, Kaur et al. 2011). Various parts of the Taxus have been used for the treatment of some noncancerous cases (Crag and Newmann 2005). Taxus baccata was also reported for the treatment of cancer. Paclitaxel is significantly active against ovarian cancer, advanced breast cancer, and lung cancer. Topotecan is used for ovarian and lung cancer from Xi shu tree [Camptotheca acuminata] (Steenhuysen 2007). Camptothecin, isolated from Camptotheca acuminate, is used for the treatment of ovarian and small cell lung cancers, and colorectal cancers (Kinghorn 1994, Creemer et al. 1996, Bertino 1997). Irinotecan is used for colon cancer treatment from Xishu tree [Camptotheca acuminate] (Online Medical Dictionary 2007). Epipodophyllotoxin was isolated as the active antitumor agent from the roots of Podophyllum species, Podophyllum peltatum and Podophyllum emodi, used in the treatment of lymphomas and bronchial and testicular cancers (Harvey 1999). The Podophyllum peltatum and P. emodii are used for the skin cancers.
Clinical characteristics and survival of extrapulmonary small cell carcinoma in 11 different primary tumor sites in the United States, 1975–2016
Published in Current Medical Research and Opinion, 2021
Treatment options for SCC were very limited and surgery was associated with improved survival time. However, some special anatomical sites had less access to surgical care, such as esophagus and pancreas. A previous study reported that surgery combined with radiotherapy significantly increased the 5 year OS rate for overall EPSCCs beside breast and genitourinary tract41. Furthermore, although radiotherapy or chemotherapy alone was beneficial to survival, the combination of the two can improve survival more37. Currently, platinum-based chemotherapy is standard first-line treatment with response rates ranging from 42% to 67% and a median OS of 15–19 months42. Temozolomide is always given in the second line. According to a NEC study of 25 patients, response rates to temozolomide with or without capecitabine and bevacizumab were 33% and median OS was 22 months when the disease progressed after platinum-based chemotherapy43. Topotecan is also recommended for second-line treatment, but evidence is lacking now. In addition, clinical trials of sunitinib and everolimus are ongoing44.
Cardiovascular safety of oncologic agents: A double-edged sword even in the era of targeted therapies – part 1
Published in Expert Opinion on Drug Safety, 2018
Antonis A. Manolis, Theodora A. Manolis, Dimitri P. Mikhailidis, Antonis S. Manolis
Topoisomerase inhibitors inhibit topoisomerase enzymes which reduce supercoiling of DNA and comprise two classes of drugs derived from natural sources, camptothecins and podophyllotoxins [121]. Their mechanism is analogous to that of the fluoroquinolone class of antibiotics. Camptothecins (topotecan, irinotecan) are plant alkaloids originally isolated from the Chinese tree Camptotheca, are S-phase specific and inhibit topoisomerase I, which is essential for the replication of DNA in human cells. Irinotecan and topotecan are semisynthetic derivatives of camptothecin. Topotecan is used in metastatic ovarian cancer and small cell lung cancer. Irinotecan is used with 5-FU and leucovorin for the treatment of colorectal carcinoma. The epipodophyllotoxin derivatives (etoposide, teniposide) inhibit topoisomerase II and their major clinical use is in the treatment of lung cancer, lymphomas and in combination with bleomycin and cisplatin for testicular carcinoma [122].
Current and future therapeutic approaches for the treatment of small cell lung cancer
Published in Expert Review of Anticancer Therapy, 2018
Antonio Rossi, Rebecca Tay, Jaseela Chiramel, Arsela Prelaj, Raffaele Califano
Topotecan, a topoisomerase-I inhibitor, is the only approved drug for second-line therapy of SCLC. However, its efficacy remains low, even in those with sensitive relapse. In a phase II study [53], 46 sensitive and 47 resistant relapsed patients were treated with 3-weekly intravenous topotecan, at the dose of 1.5 mg/m2 for five consecutive days. ORR was higher in the sensitive group compare to those with resistant relapse (37.8% vs. 6.4%); a better PFS (5.4 vs. 2.8 months) and a better OS (6.9 vs. 4.7 months) were reported for sensitive patients. In a phase III trial, 211 patients with refractory disease were randomized to intravenously topotecan versus the CAV (cyclophosphamide, doxorubicin, vincristine) regimen [54]. No differences in ORR (18.3% vs. 24.3%), PFS (3.1 vs. 3.3 months), and OS (6.2 vs. 6.3 months) were seen between topotecan and CAV. As expected, toxicities were more frequent with CAV and therefore topotecan became the preferred option. Oral topotecan, at the dose of 2.3 mg/m2 for 5 days, was compared to best supportive care (BSC) in a phase III trial and demonstrated a longer OS (6 vs. 3.2 months) [55]. Subsequently, a phase III trial compared oral versus intravenously topotecan in second-line setting [56]. Oral topotecan reported similar ORR and comparable OS to intravenously topotecan. To date, both formulations are available in the clinical practice for the second-line treatment of SCLC.