- Email: [email protected]
Carboplatin-based neoadjuvant treatment with peripheral blood stem cell and growth factor support in locally advanced cervical cancer patients with bulky metastatic lymph nodes
236
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
1.300 IU/h in continuous IV infusion) was given for 5 days continuing with enoxaparin in therapeutic doses (Clexane, Aventis Pharma 60 mg/bid SC). Two months after the delivery the patient was discharged in good condition, with peroral warfarin and recommendation for wearing elastic stockings. No signs of recurrence of DVT were registered 1 year after discharge. Our patient was a pregnant woman with history of multiple pregnancy failures, ordered with prolonged bed-rest, whose pregnancy was complicated with preeclampsia. Furthermore, she underwent a SC and developed postpartal urinary infection, all of which are well known risk factors for DVT [4]. Venous stasis normally occurring in pregnancy is mainly attributed to the compression of the iliac veins and IVC by the enlarging gravid uterus. The absence of IVC may have compromised the venous return representing an important additional risk factor for DVT. Only one case describing this vascular anomaly diagnosed during successful pregnancy was reported [5], showing similarities regarding clinical course with development of preeclampsia and IUGR. To our knowledge, our case is the first to report postpartal DVT with underlying anomaly of IVC and successful pregnancy. In conclusion, pregnant patients diagnosed with proximal thrombosis, though carrying multiple risks for DVT, should be evaluated for underlying malformations of venous system. Since direct abdominal and pelvic ionizing radiographic methods for imaging of DVT are not recommended during pregnancy, safe and conclusive procedures like ultrasound and magnetic resonance imaging should be the groundwork for reaching the final diagnosis. References [1] Chee YL, Culligan DJ, Watson HG. Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young. Br J Haematol 2001;114:878–80. [2] Obernosterer A, Aschauer M, Schnedl W, Lipp RW. Anomalies of the inferior vena cava in patients with iliac venous thrombosis. Ann Intern Med 2002;136:37–41. [3] Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis. Lancet 2001;357:441. [4] Greer IA. Prevention of venous thromboembolism in pregnancy. Best Pract Res Clin Haematol 2003;16(2):261–78. [5] Soriano D, Apter S, Dulitzky M, Oelsner G, Seidman DS. Use of magnetic resonance imaging in pregnancy to diagnose maternal malformation of inferior vena cava. Acta Obstet Gynecol Scand 1996; 75:857–9.
Marcela Ilijic* Marina Ivanisevic Josip Djelmis Department of Ob/Gyn, School of Medicine, Petrova 13, 10000 Zagreb, Croatia Miroslav Krpan Clinic for Pulmonary Diseases, Jordanovac, Zagreb, Croatia
Ljiljana Banfic Clinic for Cardiovascular Diseases, University Clinical Center, Zagreb, Croatia Mario Lusic Clinical Department of Diagnostic and Interventional Radiology, University Clinical Center, Zagreb, Croatia *Corresponding author. Tel.: +385 1 4604740; fax: +385 1 4604740 E-mail address: [email protected] (M. Ilijic) 25 June 2005 doi:10.1016/j.ejogrb.2006.04.003
Carboplatin-based neoadjuvant treatment with peripheral blood stem cell and growth factor support in locally advanced cervical cancer patients with bulky metastatic lymph nodes Dear Editor, The presence of metastatic lymphnodes is one of the major factors negatively affecting survival in cervical carcinoma [1]. These cases are commonly not included in chemoradiation or extended-field radiation protocols, and since the benefit extent of surgical removal of bulky nodes is to be clarified, neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) could represent a valuable option. Cisplatin-based regimens may achieve a high response rate in different settings and an increase in the response rate has been shown in cervical cancer when doubling the dose of cisplatin [2]. Carboplatin also has been shown to be active in cervical cancer [3], and its dose limiting toxicity (i.e. myelotoxicity) can be easily managed by growth factor (GF) and peripheral blood stem cell (PBSC) support. We investigated the efficacy and toxicity of moderately high dose carboplatin-based NACT with PBSC and GF support in histologically confirmed locally advanced cervical cancer (LACC) patients with bulky lymphnodes defined as presence of nodes >1.5 cm at the largest diameter, as assessed by magnetic resonance imaging (MRI). The study was approved by the hospital investigational review Board and written informed consent was obtained from all patients. Pre-treatment work up included clinical examination, chest radiography, abdominopelvic MRI and pathologic assessment of stage IV disease by biopsies during cystoscopy or proctoscopy, if there was a clinical suspicion of invasion. Mobilization of PBSC was performed by administering rh-G-CSF (10 mg kg 1) every day for 4 days. NACT was administered on day 1 of a 4-weekly cycle for three cycles as
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
237
Table 1 Patient characteristics and clinical outcome I.D.
Age
Histotype
Grade
Stage
Tumor size (cm)
Bulky node stations
Clinical response
Pathologic response
Overall survival (months)
Outcome
MG
44
Squamous
3
IIIB
7.4
CR
NED
54
Squamous
3
IVA
8.7
PR
Microscopic Tumor residue CR
31
ML
37
NED
MS GS LQ EM EP AC
44 46 38 36 52 35
Squamous Squamous Squamous Adeno Squamous Squamous
3 2 3 2 2 3
IVA IVA IVA IIIB IVA IIIB
7.4 5.4 4.0 4.0 6.0 6.0
SD SD SD SD SD SD
– – – – – –
19 17 12 19 11 18
DOD DOD ED ED DOD DOD
MH
50
Squamous
3
IVA
4.5
SD
–
19
DOD
MA
48
Squamous
3
IIIB
5.0
Prog
–
8
DOD
DA
56
Adeno
2
IIB
6.2
Prog
–
2
DOD
KW
63
Squamous
3
IVA
4.3
Bilateral external, internal iliac Bilateral external, internal iliac Bilateral external iliac Bilateral external iliac Monolateral external iliac Aortic Monolateral external iliac Bilateral external, internal, common iliac and aortic Bilateral external, internal and common iliac Bilateral external, internal iliac and aortic Bilateral external, internal iliac and aortic Bilateral external iliac
–
–
–
–
CR: complete response; PR: partial response; SD: stable disease; Prog: progression: DOD: death of disease, ED: alive with evidence of disease; NED: alive with no evidence of disease.
follows: carboplatin (AUC = 8), paclitaxel (175 mg/m2), epirubicin (75 mg/m2) intravenously. PBSC (1.5 106/kg CD34+ cells) were then infused and rh-G-CSF (Neupogen, Dompe` Biotec, Milan, Italy) (10 mg/kg/d s.c.) was administered from day 4 to day 13. The primary end-point of the study was the assessment of the overall response rate (OR) including complete and partial response. By employing a two-stage sampling design, an initial entry of 13 patients was planned with an additional entry if at least four responses were noted in the first stage (a = 0.05, b = 0.20). Median total carboplatin, epirubicin and paclitaxel dose per patient were 22 AUC (range 8–24), 225 mg/m2 (range 75–225) and 350 mg/m2 (175–350), respectively. Grade 3,4 leukopenia and neutropenia were observed in 30% and 36.7% of the cycles, respectively. Grade 3,4 anemia and thrombocytopenia were documented in 23.3% and in 40% of the cycles. Grade 3/4 nausea/vomiting (n = 11, 36.7%) were documented. Due to the occurrence of sepsis by Escherichia Coli and Staphiloccous Aureus in two patients, the study was prematurely stopped. Due to patient refusal (n = 1), response was evaluable in 11 patients. OR was observed in two cases (18.2%), who underwent radical surgery. Definitive pathology examination documented a complete and a microscopic partial response. The remaining unresponsive patients were administered salvage chemotherapy (n = 5) or chemoradiation (n = 4) (Table 1). Median follow-up was 17 months (range = 8–46). The two patients submitted to surgery are still alive without evidence of disease after 31 and 37 months from diagnosis. Among the seven patients with stabilization of disease, five progressed during salvage treatment and died of disease.
Considering that the OR was 18%, which is not encouraging given the toxicity of the regimen, we do not favour the delivery of high total dose platinum compounds plus PBSC and GF support in LACC patients with poor prognosis features. The availability of pre-treatment laparoscopic surgical staging, demonstrated to be highly effective in the evaluation of intrabdominal and retroperitoneal disease [4], would be of clinical relevance in selecting those poor prognosis cases who can be triaged to more aggressive surgical approaches, such as pelvic exenteration. Moreover, novel treatment strategies, such as chemosensitization, novel cytotoxic, or target-based drug combinations need to be explored. Acknowledgements This study was partly supported by Italian Association for Cancer Research (A.I.R.C.) and Cord Blood Stem Cell Project ‘‘Fondazione Cassa di Risparmio’’, Rome, Italy. References [1] Kim PY, Monk BJ, Chabra S, Burger RA, Vasilev SA, Manetta A, et al. Cervical cancer with para-aortic metastases: significance of residual paraaortic disease after surgical staging. Gynecol Oncol 1998;69: 243–7. [2] Bonomi P, Blessing JA, Stehman FB, Disaia PJ, Walton L, Major FJ. Randomised trial of three cisplatin dose schedules in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 1985;3:1079–85. [3] Papadimitriou CA, Sarris K, Moulopoulos LA, Fountzilas G, Anagnostopoulos A, Voulgaris Z, et al. Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. J Clin Oncol 1999;17:761–6.
238
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
[4] Marnitz S, Kohler C, Roth C, Fuller J, Hinkelbein W, Schneider A. Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer? Gynecol Oncol 2005;97(2):468–75.
Gabriella Ferrandina* Alessandro Perillo Mariagrazia Distefano Giuseppe D’Agostino Valerio Gallotta Gynecologic Oncology Unit, Rome, Italy Luca Pierelli Immunohematology and Transfusion Service, ASL Viterbo, Viterbo, Italy Giovanni Scambia Department of Oncology, Catholic University, Campobasso, Italy *Corresponding author at: Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy. Tel.: +39 06 35508736; fax: +39 06 35508736 E-mail address: [email protected] (G. Ferrandina) 18 October 2005 doi:10.1016/j.ejogrb.2006.04.005
Use of chemotherapy for ovarian cancer during human pregnancy: Case report and literature review Dear Editor, A 34-year-old woman, gravida 2, para 1, presented an asymptomatic adnexal mass in the right ovary (51 mm) at 9th week ultrasound examination with a stronglly vascularized bilocular structure at color doppler. CA 125 level was 751 IU/ml. At 16 weeks a further ultrasound examination for abdominopelvic pain suggested malignancy. At 17 weeks an exploratory laparotomy was performed with right salpingooophorectomy, biopsy on left ovarium, biopsy on infracolic omentum, removal of two nodules located one in the Douglas pouch and the other in the right utero-sacral ligament. The exact volume of residual disease was not ascertained.The pelvic peritoneum appeared to be macroscopically normal. Although the palpation of pelvic and paraortic lymphnodes is almost invariably inaccurate, it was in this case negative. The final histopathological diagnosis was a papillary serous cystadenocarcinoma (grade 3) and the patient was staged as having a FIGO stage IIIB. The patient wished to continue the pregnancy and a chemotherapy
regimen to control the tumor progression was proposed. Informed consent was obtained after approval of the Institutional Ethics Committee. The chemotherapy administration during pregnancy until the maturity of the fetus has been largely reported [1]. However, the use of chemotherapy in pregnant patients with epithelial ovarian cancer is very rare: only 11 cases have been reported to date [2–5] and all patients for whom the stage was reported had stage III disease. Even though the combination of cisplatin (or carboplatin) plus paclitaxel is the reference regimen outside pregnancy, notwithstanding that the combination of paclitaxel and carboplatin was used by Mendez et al. [6] and that paclitaxel plus cisplatin was used by Sood et al. [7] also during pregnancy, we thought that it could be too toxic and potentially dangerous for the fetus. The use of one drug alone, and in the specific case paclitaxel, was preferred due to the toxicities reported for platinum agents. Regarding the specific toxicities of carboplatin and cisplatin, carboplatin is more likely to cause trombocytopenia and it is less proteinbound than cisplatin, possibly favoring placenta transfer. Regarding cisplatin, sensorineural hearing loss was reported in a child of 1 year of age who had been exposed to cisplatin in utero [8]. Therefore, it was decided to treat our patient with paclitaxel alone. It is worthy of note that the use of paclitaxel in human pregnancy has rarely been reported and, moreover, this is, to our knowledge, the first published case of the use of paclitaxel alone for chemotherapy of epithelial ovarian cancer during pregnancy. Chemotherapy treatment was postponed until the 22nd week in order to minimize fetal risks. Paclitaxel 175 mg/m2 day 1 q 21 was administered for five courses at the same dosage for a total of 875 mg/m2, the last being on week 35, without significant side effects. CA 125 levels decreased to normal. Fetal well-being was assessed throughout chemotherapy. At 38th week the fetal maturation was complete at ultrasound and caesarean section was performed because of premature membrane rupture. A healthy baby (2.490 kg) was delivered, with an Apgar score of 9 and 10 at 1 and 5 min, respectively. The placenta was macroscopically and histologically normal. The surgical oncology procedure included exploration of the abdominal cavity, total hysterectomy, left salpingo-oophorectomy, removal of the superior third of the vagina, full omentectomy, pelvic lymphadenectomy (common iliac, internal iliac and obturatory, bilaterally), appendectomy, and several peritonectomies. Peritoneal cytology was negative. Lombo-aortic lymphnodes appeared macroscopically not involved and no sample was removed. No peri- or post-operative major complications were observed. Histological examination revealed no evidence of tumour in the residual left ovarian parenchima, the presence of focal neoplastic thrombosis in the lymphatic vessels surrounding the uterus, one metastatic lymphnode out of seven sampled of the left obturatory nodes, plus foci of serous carcinoma in the mesosalpynx. The final pathological stage was IIIC. No residual
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
1.300 IU/h in continuous IV infusion) was given for 5 days continuing with enoxaparin in therapeutic doses (Clexane, Aventis Pharma 60 mg/bid SC). Two months after the delivery the patient was discharged in good condition, with peroral warfarin and recommendation for wearing elastic stockings. No signs of recurrence of DVT were registered 1 year after discharge. Our patient was a pregnant woman with history of multiple pregnancy failures, ordered with prolonged bed-rest, whose pregnancy was complicated with preeclampsia. Furthermore, she underwent a SC and developed postpartal urinary infection, all of which are well known risk factors for DVT [4]. Venous stasis normally occurring in pregnancy is mainly attributed to the compression of the iliac veins and IVC by the enlarging gravid uterus. The absence of IVC may have compromised the venous return representing an important additional risk factor for DVT. Only one case describing this vascular anomaly diagnosed during successful pregnancy was reported [5], showing similarities regarding clinical course with development of preeclampsia and IUGR. To our knowledge, our case is the first to report postpartal DVT with underlying anomaly of IVC and successful pregnancy. In conclusion, pregnant patients diagnosed with proximal thrombosis, though carrying multiple risks for DVT, should be evaluated for underlying malformations of venous system. Since direct abdominal and pelvic ionizing radiographic methods for imaging of DVT are not recommended during pregnancy, safe and conclusive procedures like ultrasound and magnetic resonance imaging should be the groundwork for reaching the final diagnosis. References [1] Chee YL, Culligan DJ, Watson HG. Inferior vena cava malformation as a risk factor for deep venous thrombosis in the young. Br J Haematol 2001;114:878–80. [2] Obernosterer A, Aschauer M, Schnedl W, Lipp RW. Anomalies of the inferior vena cava in patients with iliac venous thrombosis. Ann Intern Med 2002;136:37–41. [3] Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis. Lancet 2001;357:441. [4] Greer IA. Prevention of venous thromboembolism in pregnancy. Best Pract Res Clin Haematol 2003;16(2):261–78. [5] Soriano D, Apter S, Dulitzky M, Oelsner G, Seidman DS. Use of magnetic resonance imaging in pregnancy to diagnose maternal malformation of inferior vena cava. Acta Obstet Gynecol Scand 1996; 75:857–9.
Marcela Ilijic* Marina Ivanisevic Josip Djelmis Department of Ob/Gyn, School of Medicine, Petrova 13, 10000 Zagreb, Croatia Miroslav Krpan Clinic for Pulmonary Diseases, Jordanovac, Zagreb, Croatia
Ljiljana Banfic Clinic for Cardiovascular Diseases, University Clinical Center, Zagreb, Croatia Mario Lusic Clinical Department of Diagnostic and Interventional Radiology, University Clinical Center, Zagreb, Croatia *Corresponding author. Tel.: +385 1 4604740; fax: +385 1 4604740 E-mail address: [email protected] (M. Ilijic) 25 June 2005 doi:10.1016/j.ejogrb.2006.04.003
Carboplatin-based neoadjuvant treatment with peripheral blood stem cell and growth factor support in locally advanced cervical cancer patients with bulky metastatic lymph nodes Dear Editor, The presence of metastatic lymphnodes is one of the major factors negatively affecting survival in cervical carcinoma [1]. These cases are commonly not included in chemoradiation or extended-field radiation protocols, and since the benefit extent of surgical removal of bulky nodes is to be clarified, neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) could represent a valuable option. Cisplatin-based regimens may achieve a high response rate in different settings and an increase in the response rate has been shown in cervical cancer when doubling the dose of cisplatin [2]. Carboplatin also has been shown to be active in cervical cancer [3], and its dose limiting toxicity (i.e. myelotoxicity) can be easily managed by growth factor (GF) and peripheral blood stem cell (PBSC) support. We investigated the efficacy and toxicity of moderately high dose carboplatin-based NACT with PBSC and GF support in histologically confirmed locally advanced cervical cancer (LACC) patients with bulky lymphnodes defined as presence of nodes >1.5 cm at the largest diameter, as assessed by magnetic resonance imaging (MRI). The study was approved by the hospital investigational review Board and written informed consent was obtained from all patients. Pre-treatment work up included clinical examination, chest radiography, abdominopelvic MRI and pathologic assessment of stage IV disease by biopsies during cystoscopy or proctoscopy, if there was a clinical suspicion of invasion. Mobilization of PBSC was performed by administering rh-G-CSF (10 mg kg 1) every day for 4 days. NACT was administered on day 1 of a 4-weekly cycle for three cycles as
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
237
Table 1 Patient characteristics and clinical outcome I.D.
Age
Histotype
Grade
Stage
Tumor size (cm)
Bulky node stations
Clinical response
Pathologic response
Overall survival (months)
Outcome
MG
44
Squamous
3
IIIB
7.4
CR
NED
54
Squamous
3
IVA
8.7
PR
Microscopic Tumor residue CR
31
ML
37
NED
MS GS LQ EM EP AC
44 46 38 36 52 35
Squamous Squamous Squamous Adeno Squamous Squamous
3 2 3 2 2 3
IVA IVA IVA IIIB IVA IIIB
7.4 5.4 4.0 4.0 6.0 6.0
SD SD SD SD SD SD
– – – – – –
19 17 12 19 11 18
DOD DOD ED ED DOD DOD
MH
50
Squamous
3
IVA
4.5
SD
–
19
DOD
MA
48
Squamous
3
IIIB
5.0
Prog
–
8
DOD
DA
56
Adeno
2
IIB
6.2
Prog
–
2
DOD
KW
63
Squamous
3
IVA
4.3
Bilateral external, internal iliac Bilateral external, internal iliac Bilateral external iliac Bilateral external iliac Monolateral external iliac Aortic Monolateral external iliac Bilateral external, internal, common iliac and aortic Bilateral external, internal and common iliac Bilateral external, internal iliac and aortic Bilateral external, internal iliac and aortic Bilateral external iliac
–
–
–
–
CR: complete response; PR: partial response; SD: stable disease; Prog: progression: DOD: death of disease, ED: alive with evidence of disease; NED: alive with no evidence of disease.
follows: carboplatin (AUC = 8), paclitaxel (175 mg/m2), epirubicin (75 mg/m2) intravenously. PBSC (1.5 106/kg CD34+ cells) were then infused and rh-G-CSF (Neupogen, Dompe` Biotec, Milan, Italy) (10 mg/kg/d s.c.) was administered from day 4 to day 13. The primary end-point of the study was the assessment of the overall response rate (OR) including complete and partial response. By employing a two-stage sampling design, an initial entry of 13 patients was planned with an additional entry if at least four responses were noted in the first stage (a = 0.05, b = 0.20). Median total carboplatin, epirubicin and paclitaxel dose per patient were 22 AUC (range 8–24), 225 mg/m2 (range 75–225) and 350 mg/m2 (175–350), respectively. Grade 3,4 leukopenia and neutropenia were observed in 30% and 36.7% of the cycles, respectively. Grade 3,4 anemia and thrombocytopenia were documented in 23.3% and in 40% of the cycles. Grade 3/4 nausea/vomiting (n = 11, 36.7%) were documented. Due to the occurrence of sepsis by Escherichia Coli and Staphiloccous Aureus in two patients, the study was prematurely stopped. Due to patient refusal (n = 1), response was evaluable in 11 patients. OR was observed in two cases (18.2%), who underwent radical surgery. Definitive pathology examination documented a complete and a microscopic partial response. The remaining unresponsive patients were administered salvage chemotherapy (n = 5) or chemoradiation (n = 4) (Table 1). Median follow-up was 17 months (range = 8–46). The two patients submitted to surgery are still alive without evidence of disease after 31 and 37 months from diagnosis. Among the seven patients with stabilization of disease, five progressed during salvage treatment and died of disease.
Considering that the OR was 18%, which is not encouraging given the toxicity of the regimen, we do not favour the delivery of high total dose platinum compounds plus PBSC and GF support in LACC patients with poor prognosis features. The availability of pre-treatment laparoscopic surgical staging, demonstrated to be highly effective in the evaluation of intrabdominal and retroperitoneal disease [4], would be of clinical relevance in selecting those poor prognosis cases who can be triaged to more aggressive surgical approaches, such as pelvic exenteration. Moreover, novel treatment strategies, such as chemosensitization, novel cytotoxic, or target-based drug combinations need to be explored. Acknowledgements This study was partly supported by Italian Association for Cancer Research (A.I.R.C.) and Cord Blood Stem Cell Project ‘‘Fondazione Cassa di Risparmio’’, Rome, Italy. References [1] Kim PY, Monk BJ, Chabra S, Burger RA, Vasilev SA, Manetta A, et al. Cervical cancer with para-aortic metastases: significance of residual paraaortic disease after surgical staging. Gynecol Oncol 1998;69: 243–7. [2] Bonomi P, Blessing JA, Stehman FB, Disaia PJ, Walton L, Major FJ. Randomised trial of three cisplatin dose schedules in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 1985;3:1079–85. [3] Papadimitriou CA, Sarris K, Moulopoulos LA, Fountzilas G, Anagnostopoulos A, Voulgaris Z, et al. Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. J Clin Oncol 1999;17:761–6.
238
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 131 (2007) 235–245
[4] Marnitz S, Kohler C, Roth C, Fuller J, Hinkelbein W, Schneider A. Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer? Gynecol Oncol 2005;97(2):468–75.
Gabriella Ferrandina* Alessandro Perillo Mariagrazia Distefano Giuseppe D’Agostino Valerio Gallotta Gynecologic Oncology Unit, Rome, Italy Luca Pierelli Immunohematology and Transfusion Service, ASL Viterbo, Viterbo, Italy Giovanni Scambia Department of Oncology, Catholic University, Campobasso, Italy *Corresponding author at: Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy. Tel.: +39 06 35508736; fax: +39 06 35508736 E-mail address: [email protected] (G. Ferrandina) 18 October 2005 doi:10.1016/j.ejogrb.2006.04.005
Use of chemotherapy for ovarian cancer during human pregnancy: Case report and literature review Dear Editor, A 34-year-old woman, gravida 2, para 1, presented an asymptomatic adnexal mass in the right ovary (51 mm) at 9th week ultrasound examination with a stronglly vascularized bilocular structure at color doppler. CA 125 level was 751 IU/ml. At 16 weeks a further ultrasound examination for abdominopelvic pain suggested malignancy. At 17 weeks an exploratory laparotomy was performed with right salpingooophorectomy, biopsy on left ovarium, biopsy on infracolic omentum, removal of two nodules located one in the Douglas pouch and the other in the right utero-sacral ligament. The exact volume of residual disease was not ascertained.The pelvic peritoneum appeared to be macroscopically normal. Although the palpation of pelvic and paraortic lymphnodes is almost invariably inaccurate, it was in this case negative. The final histopathological diagnosis was a papillary serous cystadenocarcinoma (grade 3) and the patient was staged as having a FIGO stage IIIB. The patient wished to continue the pregnancy and a chemotherapy
regimen to control the tumor progression was proposed. Informed consent was obtained after approval of the Institutional Ethics Committee. The chemotherapy administration during pregnancy until the maturity of the fetus has been largely reported [1]. However, the use of chemotherapy in pregnant patients with epithelial ovarian cancer is very rare: only 11 cases have been reported to date [2–5] and all patients for whom the stage was reported had stage III disease. Even though the combination of cisplatin (or carboplatin) plus paclitaxel is the reference regimen outside pregnancy, notwithstanding that the combination of paclitaxel and carboplatin was used by Mendez et al. [6] and that paclitaxel plus cisplatin was used by Sood et al. [7] also during pregnancy, we thought that it could be too toxic and potentially dangerous for the fetus. The use of one drug alone, and in the specific case paclitaxel, was preferred due to the toxicities reported for platinum agents. Regarding the specific toxicities of carboplatin and cisplatin, carboplatin is more likely to cause trombocytopenia and it is less proteinbound than cisplatin, possibly favoring placenta transfer. Regarding cisplatin, sensorineural hearing loss was reported in a child of 1 year of age who had been exposed to cisplatin in utero [8]. Therefore, it was decided to treat our patient with paclitaxel alone. It is worthy of note that the use of paclitaxel in human pregnancy has rarely been reported and, moreover, this is, to our knowledge, the first published case of the use of paclitaxel alone for chemotherapy of epithelial ovarian cancer during pregnancy. Chemotherapy treatment was postponed until the 22nd week in order to minimize fetal risks. Paclitaxel 175 mg/m2 day 1 q 21 was administered for five courses at the same dosage for a total of 875 mg/m2, the last being on week 35, without significant side effects. CA 125 levels decreased to normal. Fetal well-being was assessed throughout chemotherapy. At 38th week the fetal maturation was complete at ultrasound and caesarean section was performed because of premature membrane rupture. A healthy baby (2.490 kg) was delivered, with an Apgar score of 9 and 10 at 1 and 5 min, respectively. The placenta was macroscopically and histologically normal. The surgical oncology procedure included exploration of the abdominal cavity, total hysterectomy, left salpingo-oophorectomy, removal of the superior third of the vagina, full omentectomy, pelvic lymphadenectomy (common iliac, internal iliac and obturatory, bilaterally), appendectomy, and several peritonectomies. Peritoneal cytology was negative. Lombo-aortic lymphnodes appeared macroscopically not involved and no sample was removed. No peri- or post-operative major complications were observed. Histological examination revealed no evidence of tumour in the residual left ovarian parenchima, the presence of focal neoplastic thrombosis in the lymphatic vessels surrounding the uterus, one metastatic lymphnode out of seven sampled of the left obturatory nodes, plus foci of serous carcinoma in the mesosalpynx. The final pathological stage was IIIC. No residual