Bell DR, Woods RL, Levi JA. Acute leukaemia after alkylating-agent therapy of ovarian cancer.Med J Aust. 1982 Sep 4;2(5):243-4. No abstract available.PMID: 7132879 [PubMed - indexed for MEDLINE]
Blythe JC. Acute leukemia after melphalan treatment for ovarian carcinoma.J Med Assoc State Ala. 1977 Nov;47(5):42-3, 57. No abstract available.PMID: 925549 [PubMed - indexed for MEDLINE]
Colon-Otero G, Malkasian GD, Edmonson JH. Secondary myelodysplasia and acute leukemia following carboplatin-containing combination chemotherapy for ovarian cancer.J Natl Cancer Inst. 1993 Nov 17;85(22):1858-60. No abstract available.PMID: 8230267 [PubMed - indexed for MEDLINE]
Gramont A, Remes P, Krulik M, Smadja N, Drolet Y, Donadio D, Louvet C, Brissaud P,
Sirinelli A, Dray C, et al.Acute leukemia after treatment for ovarian
cancer. Report of four cases and review of the literature.Oncology.
1986;43(3):165-72.PMID: 3703462 [PubMed - indexed for MEDLINE]
Four cases of acute nonlymphocytic leukemia (ANLL) following ovarian cancer are reported. All patients received alkylating agents and had a preleukemic phase. Seventy-nine additional cases of ANLL following therapy found in the literature are also reviewed. All but 2 patients received alkylating or alkylating-related agents alone or in combination. Mean duration of chemotherapy was 31.4 +/- 19.4 months. Eighty-eight percent of the patients presented with preleukemia with a mean duration of 10 +/- 10 months. Mean interval between cancer and ANLL was 57.3 +/- 26 months. Cytogenetic abnormalities were found in 71% among patients who had a karyotype. Long-term alkylating agent therapy seems to have a significant role in the development of ANLL and should be avoided in ovarian cancer.
Greene MH, Boice JD Jr, Greer BE, Blessing JA, Dembo AJ. Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials.N Engl J Med. 1982 Dec 2;307(23):1416-21.PMID: 6752720 [PubMed - indexed for MEDLINE]
Izumi R, Kawabata M, Nagasaka T. [Chemotherapy for ovarian cancer--drug selection and induced acute leukemia]Nippon Sanka Fujinka Gakkai Zasshi. 1984 Feb;36(2):311-6. Japanese. No abstract available.PMID: 6321617 [PubMed - indexed for MEDLINE]
SB, Krause JR. Ovarian carcinoma terminating in acute
nonlymphocytic leukemia following alkylating agent therapy.
Cancer. 1978 May;41(5):1676-9. Review.PMID: 417794 [PubMed - indexed for MEDLINE]
JD, Kurtides ES, Stalzer RC. Acute erythroleukemia complicating
prolonged chemotherapy for ovarian carcinoma.
Arch Intern Med. 1977 Mar;137(3):355-6.PMID: 402895 [PubMed - indexed for MEDLINE]
Kagan AR, Ryoo MC, Tawa K, Saltz A. Secondary neoplasms in treated ovarian cancer.Gynecol Oncol. 1982 Jun;13(3):356-64. No abstract available.PMID: 7095575 [PubMed - indexed for MEDLINE]
Kaldor JM, Day NE, Pettersson F, Clarke EA, Pedersen D, Mehnert W, Bell J, Host H, Prior P, Karjalainen S, et al. Leukemia following chemotherapy for ovarian cancer.N Engl J Med. 1990 Jan 4;322(1):1-6.PMID: 2104664 [PubMed - indexed for MEDLINE]
JM, Day NE, Kittelmann B, Pettersson F, Langmark F, Pedersen D, Prior P, Neal F,
Karjalainen S, Bell J, et al. Bladder tumours following chemotherapy and
radiotherapy for ovarian cancer: a case-control study.Int J Cancer.
1995 Sep 27;63(1):1-6.PMID: 7558434 [PubMed - indexed for MEDLINE]
A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.
Littleton RE, Homesley HD, Richards F 2nd. Leukemogenesis related to chemotherapy of ovarian carcinoma: a review with three new case reports.Gynecol Oncol. 1984 Nov;19(3):268-77. Review.PMID: 6389274 [PubMed - indexed for MEDLINE]
A review of the literature of 68 case reports of acute leukemia following ovarian cancer is presented and 3 new cases are reported. Review of the literature revealed 34 patients received chemotherapy and radiotherapy, 32 patients received chemotherapy alone, 1 patient had only surgery, and the radiation status of the remaining patient is unclear. Chemotherapy usually consisted of alkylating agents often given in high dose and for long durations. The reported risk for developing acute leukemia after treatment of ovarian cancer ranges from 21 to 175 times that of the general population with a prevalence range in treated patients of 0.8 to 2.7%. The median interval from initiation of therapy to the development of leukemia is shortened from 54.2 to 41.1 months if radiation therapy is used in addition to chemotherapy. The patients typically exhibit a brief preleukemic phase and poor survival with death occurring 3 to 5 months after diagnosis of leukemia. Proposed mechanisms for leukemogenesis are presented.
Parker LM. Leukemia after treatment of ovarian cancer with alkylating agents.N Engl J Med. 1983 Jun 9;308(23):1422. No abstract available.PMID: 6843637 [PubMed - indexed for MEDLINE]
Reimer RR, Hoover R, Fraumeni JF Jr, Young RC. Acute leukemia after alkylating-agent therapy of ovarian cancer.N Engl J Med. 1977 Jul 28;297(4):177-81.PMID: 406560 [PubMed - indexed for MEDLINE]
G, Jafari K, Lash AF, Stepto RC. Acute leukemia in advanced
ovarian carcinoma after treatment with alkylating agents.
Obstet Gynecol. 1976 Jan;47(1):67S-71S.PMID: 1061006 [PubMed - indexed for MEDLINE]
Sprance HE, Hempling RE, Piver MS. Leukemia following cisplatin-based chemotherapy for ovarian carcinoma at Roswell Park.Eur J Gynaecol Oncol. 1992;13(2):131-7.PMID: 1587290 [PubMed - indexed for MEDLINE]
Travis LB, Risk of leukemia after platinum-based chemotherapy for ovarian cancer.N Engl J Med. 1999 Feb 4;340(5):351-7.PMID: 9929525 [PubMed - indexed for MEDLINE]
BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia.
Tucker MA, Fraumeni JF Jr. Treatment-related cancers after gynecologic malignancy.Cancer. 1987 Oct 15;60(8 Suppl):2117-22. Review.PMID: 3308071 [PubMed - indexed for MEDLINE]
F, Tubiana-Hulin M, Meeus L, Goupil A, Berlie J, Clavel B.
[Complications of antitumor and antileukemia chemotherapy. 3 (conclusion)]Sem Hop. 1982 Nov 4;58(40):2303-13. Review. French.PMID: 6297011 [PubMed -
indexed for MEDLINE]
Among the neurological side-effects, peripheral neuropathy is a result of therapy with vindesine and above all vincristine. Although in most cases it is responsible only for paresthesias, it may cause extensive paralysis and requires that the drug be discontinued. These drugs may also affect the neurovegetative system. Ototoxicity may be seen with cis-platinum and vigilance disturbances with L-asparaginase. Genetic consequences are mainly due to alkylating agents. These agents almost constantly impair male and female fertility but recovery is possible. Libido is also affected with the attendant psychological consequences. The offspring of patients previously treated by chemotherapeutic agents are normal. Development of secondary carcinoma or leukemia is currently a major concern. Secondary malignant disease may develop after the treatment of any cancer, especially if radiotherapy was associated with alkylating agents. Leukemias are of the acute myeloid type and usually follow a preleukemic phase. A table summarizes the main toxicities of the most usual drugs.
Thigpen JT, Bertelsen K, Eisenhauer EA, Hacker NF, Lund B, Sessa C. Long-term follow-up of patients with advanced ovarian carcinoma treated with chemotherapy.Ann Oncol. 1993;4 Suppl 4:35-40. Review.PMID: 8312199 [PubMed - indexed for MEDLINE]
Vogl SE, Pagano M, Kaplan BH, Einhorn N, Arseneau J, Moukhtar M, Greenwald E. Combination chemotherapy of advanced ovarian cancer with hexamethylmelamine, cis-Platinum, and doxorubicin after failure of prior therapy.Obstet Gynecol. 1980 Nov;56(5):635-40.PMID: 6776457 [PubMed - indexed for MEDLINE]
Forty-nine women received a combination of cis-platinum and hexamethylmelamine (36 also received doxorubicin) for advanced ovarian cancer progressing after therapy that included an alkylating agent or extended field radiation. Twenty-six (53%) had an objective remission that lasted a median of 6 months from start of treatment. Response rate was independent of age, extent of prior therapy, and performance status. A long interval from initial diagnosis to entry, response to therapy, and ambulatory performance predicted improved survival from entry. No patient is surviving free of disease. Myelosuppression and vomiting were moderately severe but tolerable. Azotemia and peripheral neuropathy were infrequent and milk. These drugs have major activity in this poor-risk group and should be studied as part of initial therapy when enhanced efficacy and reduced toxicity are to be expected.