Risk for premature menopause in women treated for Hodgkin lymphoma with various chemotherapeutic agents, compared with women who were treated with radiotherapy only, provided the ovaries were not located in the radiation fields
| . | Patients, no.* (n = 518) . | % . | Events, no. (n = 97) . | Py (n = 4989) . | Events/1000 Py . | HR (95% CI) . |
|---|---|---|---|---|---|---|
| RT alone | 245 | 47 | 6 | 2426 | 2 | 1 (ref) |
| CT classes‡ | ||||||
| Alkylating agents, yes/no | 276 | 53 | 85 | 2130 | 40 | 6.1 (2.7-13.7) |
| Antimetabolites, yes/no | 12 | 2 | 7 | 66 | 105 | 1.4 (0.3-7.9) |
| Antimitotic agents, yes/no | 302 | 58 | 80 | 2538 | 31 | 0.6 (0.3-1.4) |
| Antitumor antibiotics, yes/no | 150 | 29 | 29 | 1188 | 24 | 0.5 (0.3-0.9) |
| Topoisomerase inhibitors, yes/no | 20 | 4 | 10 | 98 | 102 | 1.6 (0.6-4.3) |
| Antimitotic agents§ | ||||||
| Vincristine, yes/no | 234 | 45 | 77 | 1725 | 45 | 1.6 (0.7-3.6) |
| Vinblastine, yes/no | 183 | 35 | 31 | 1567 | 20 | 0.5 (0.2-1.4) |
| Antitumor antibiotics‖ | ||||||
| Doxorubicin, yes/no | 119 | 23 | 22 | 934 | 24 | 0.4 (0.2-1.1) |
| Bleomycin, yes/no | 146 | 28 | 27 | 1170 | 23 | 1.0 (0.4-2.4) |
| Alkylating agents | ||||||
| Procarbazine, yes/no¶ | 239 | 46 | 78 | 1770 | 44 | 8.1 (2.0-32.8) |
| 4.2 g/m2 or less#** | 98 | 19 | 13 | 753 | 23 | 1.3 (0.2-6.8) |
| 4.2 to 8.4 g/m2# | 90 | 17 | 32 | 691 | 46 | 5.2 (1.6-17.1) |
| More than 8.4 g/m2#†† | 48 | 9 | 26 | 205 | 127 | 20.4 (4.4-93.6) |
| Exact amount unknown | 13 | 3 | 7 | 121 | 58 | 5.9 (1.6-22.4) |
| Mechlorethamine, yes/no¶ | 239 | 46 | 75 | 1763 | 43 | 1.6 (0.6-4.0) |
| 36 mg/m2 or less#** | 101 | 19 | 16 | 779 | 26 | 2.6 (0.6-10.5) |
| 36 to 72 mg/m2# | 93 | 18 | 32 | 701 | 46 | 1.3 (0.5-3.3) |
| More than 72 mg/m2#‡‡ | 42 | 8 | 22 | 208 | 106 | 0.8 (0.2-3.3) |
| Exact amount unknown | 13 | 3 | 5 | 76 | 66 | 1.0 (0.3-3.6) |
| Cyclophosphamide, yes/no¶ | 40 | 8 | 24 | 243 | 99 | 3.5 (2.0-5.9) |
| Dacarbazine, yes/no¶ | 27 | 5 | 2 | 269 | 7 | 0.3 (0.1-1.5) |
| Lomustine, yes/no¶ | 25 | 5 | 9 | 80 | 112 | 1.6 (0.7-3.6) |
| Chlorambucil, yes/no¶ | 16 | 3 | 10 | 77 | 130 | 2.0 (0.8-4.7) |
| Carmustine, yes/no¶ | 7 | 1 | 4 | 36 | 111 | 0.7 (0.1-3.7) |
| Ifosfamide, yes/no¶ | 4 | 1 | 2 | 18 | 111 | 1.3 (0.2-10.3) |
| Mutually exclusive CT categories‡** | ||||||
| No CT | 289 | 56 | 6 | 2248 | 3 | 1 (ref) |
| Nonalkylating CT only | 45 | 9 | 1 | 465 | 2 | 0.8 (0.1-6.9) |
| Alkylating CT, no procarbazine | 46 | 9 | 5 | 360 | 14 | 5.4 (1.6-18.2) |
| Alkylating CT, 8.4 g/m2 or less procarbazine | 183 | 35 | 44 | 1444 | 30 | 10.9 (4.6-26.1) |
| Alkylating CT, more than 8.4 g/m2 procarbazine | 48 | 9 | 26 | 205 | 127 | 41.5 (16.9-102) |
| . | Patients, no.* (n = 518) . | % . | Events, no. (n = 97) . | Py (n = 4989) . | Events/1000 Py . | HR (95% CI) . |
|---|---|---|---|---|---|---|
| RT alone | 245 | 47 | 6 | 2426 | 2 | 1 (ref) |
| CT classes‡ | ||||||
| Alkylating agents, yes/no | 276 | 53 | 85 | 2130 | 40 | 6.1 (2.7-13.7) |
| Antimetabolites, yes/no | 12 | 2 | 7 | 66 | 105 | 1.4 (0.3-7.9) |
| Antimitotic agents, yes/no | 302 | 58 | 80 | 2538 | 31 | 0.6 (0.3-1.4) |
| Antitumor antibiotics, yes/no | 150 | 29 | 29 | 1188 | 24 | 0.5 (0.3-0.9) |
| Topoisomerase inhibitors, yes/no | 20 | 4 | 10 | 98 | 102 | 1.6 (0.6-4.3) |
| Antimitotic agents§ | ||||||
| Vincristine, yes/no | 234 | 45 | 77 | 1725 | 45 | 1.6 (0.7-3.6) |
| Vinblastine, yes/no | 183 | 35 | 31 | 1567 | 20 | 0.5 (0.2-1.4) |
| Antitumor antibiotics‖ | ||||||
| Doxorubicin, yes/no | 119 | 23 | 22 | 934 | 24 | 0.4 (0.2-1.1) |
| Bleomycin, yes/no | 146 | 28 | 27 | 1170 | 23 | 1.0 (0.4-2.4) |
| Alkylating agents | ||||||
| Procarbazine, yes/no¶ | 239 | 46 | 78 | 1770 | 44 | 8.1 (2.0-32.8) |
| 4.2 g/m2 or less#** | 98 | 19 | 13 | 753 | 23 | 1.3 (0.2-6.8) |
| 4.2 to 8.4 g/m2# | 90 | 17 | 32 | 691 | 46 | 5.2 (1.6-17.1) |
| More than 8.4 g/m2#†† | 48 | 9 | 26 | 205 | 127 | 20.4 (4.4-93.6) |
| Exact amount unknown | 13 | 3 | 7 | 121 | 58 | 5.9 (1.6-22.4) |
| Mechlorethamine, yes/no¶ | 239 | 46 | 75 | 1763 | 43 | 1.6 (0.6-4.0) |
| 36 mg/m2 or less#** | 101 | 19 | 16 | 779 | 26 | 2.6 (0.6-10.5) |
| 36 to 72 mg/m2# | 93 | 18 | 32 | 701 | 46 | 1.3 (0.5-3.3) |
| More than 72 mg/m2#‡‡ | 42 | 8 | 22 | 208 | 106 | 0.8 (0.2-3.3) |
| Exact amount unknown | 13 | 3 | 5 | 76 | 66 | 1.0 (0.3-3.6) |
| Cyclophosphamide, yes/no¶ | 40 | 8 | 24 | 243 | 99 | 3.5 (2.0-5.9) |
| Dacarbazine, yes/no¶ | 27 | 5 | 2 | 269 | 7 | 0.3 (0.1-1.5) |
| Lomustine, yes/no¶ | 25 | 5 | 9 | 80 | 112 | 1.6 (0.7-3.6) |
| Chlorambucil, yes/no¶ | 16 | 3 | 10 | 77 | 130 | 2.0 (0.8-4.7) |
| Carmustine, yes/no¶ | 7 | 1 | 4 | 36 | 111 | 0.7 (0.1-3.7) |
| Ifosfamide, yes/no¶ | 4 | 1 | 2 | 18 | 111 | 1.3 (0.2-10.3) |
| Mutually exclusive CT categories‡** | ||||||
| No CT | 289 | 56 | 6 | 2248 | 3 | 1 (ref) |
| Nonalkylating CT only | 45 | 9 | 1 | 465 | 2 | 0.8 (0.1-6.9) |
| Alkylating CT, no procarbazine | 46 | 9 | 5 | 360 | 14 | 5.4 (1.6-18.2) |
| Alkylating CT, 8.4 g/m2 or less procarbazine | 183 | 35 | 44 | 1444 | 30 | 10.9 (4.6-26.1) |
| Alkylating CT, more than 8.4 g/m2 procarbazine | 48 | 9 | 26 | 205 | 127 | 41.5 (16.9-102) |
Patients may contribute person-time to more than one category; numbers do not add up.
Adjusted for smoking, oral contraceptive use, dose-level of radiotherapy, age at first treatment, and other variables; age was used as the time scale.
§Adjusted for smoking, oral contraceptive use, dose-level of radiotherapy, age at first treatment, other variables, and other chemotherapy (alkylating agents: yes/no, antimetabolites: yes/no, antitumor antibiotics: yes/no, topoisomerase inhibitors: yes/no, other chemotherapy: yes/no); age was used as the time scale.
Adjusted for smoking, oral contraceptive use, dose level of radiotherapy, age at first treatment, other variables, and other chemotherapy (alkylating agents: yes/no, antimetabolites: yes/no, antitumor antibiotics: yes/no, antimitotic agents: yes/no, topoisomerase inhibitors: yes/no, other chemotherapy: yes/no); age was used as the time scale.
Adjusted for smoking, oral contraceptive use, dose level of radiotherapy, age at first treatment, other variables, and other chemotherapy (antimitotic agents: yes/no; antitumor antibiotics: yes/no; unknown chemotherapy regimen: yes/no; antimetabolites, topoisomerase inhibitors, or other chemotherapy: yes/no); age was used as the time scale.
Adjusted for smoking, oral contraceptive use, dose level of radiotherapy, age at first treatment, other variables, and other chemotherapy (cyclophosphamide: yes/no, other alkylating chemotherapy: yes/no, other nonalkylating chemotherapy: yes/no, unknown chemotherapy regimen: yes/no); age was used as the time scale.
One cycle of MOPP contains 1.4 g/m2 procarbazine and 12 mg/m2 mechlorethamine; one cycle of MOPP/ABV contains 0.7 g/m2 procarbazine and 6 mg/m2 mechlorethamine; one cycle of BEACOPP (baseline or escalated) contains 0.7 g/m2 procarbazine.
P-trend is .02. Based on the slope of continuous number of cycles of a given regimen among those treated with that regimen.
P-trend is .90. Based on the slope of continuous number of cycles of a given regimen among those treated with that regimen.