Trial Outcomes & Findings for Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma (NCT NCT01132807)

Last Updated: 2021-06-14

Results Overview

The primary objective of this trial is to estimate the 3 year PFS in patients who received 4 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, all patients that received 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) are included.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

164 participants

Primary outcome timeframe

36 Months

Results posted on

2021-06-14

Participant Flow

Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. PET/CT central review occurred after cycle 2. PET-negative patients received 2 additional cycles of ABVD. PET-positive patients received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP.

Participant milestones

Participant milestones
Measure	Treatment (ABVD:Additional 2 Cycles) Therapy consisted of an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.\> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15\> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle.	Only Initial ABVD Treatment Therapy consisted of 2 initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.\> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15	Escalated BEACOPP and Involved Field Radiation Therapy Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. \> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15\> \>\> \> \>\> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP:\> \>\> \> \>\> Bleomycin 10 units/m2 IV on Day 8\> \>\> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \> \>\> Doxorubicin 35 mg/m2 IV on Day 1 \> \>\> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \> \>\> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \> \>\> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7\> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Initial ABVD Treatment (2 Cycles) STARTED	135	15	14
Initial ABVD Treatment (2 Cycles) COMPLETED	135	0	14
Initial ABVD Treatment (2 Cycles) NOT COMPLETED	0	15	0
Post-Cycle 2 PET Assessment STARTED	135	0	14
Post-Cycle 2 PET Assessment COMPLETED	135	0	14
Post-Cycle 2 PET Assessment NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (ABVD:Additional 2 Cycles) Therapy consisted of an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.\> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15\> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle.	Only Initial ABVD Treatment Therapy consisted of 2 initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.\> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15	Escalated BEACOPP and Involved Field Radiation Therapy Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. \> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\> * Bleomycin 10 units/m2 IV on Days 1 and 15\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15\> \>\> \> \>\> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP:\> \>\> \> \>\> Bleomycin 10 units/m2 IV on Day 8\> \>\> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \> \>\> Doxorubicin 35 mg/m2 IV on Day 1 \> \>\> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \> \>\> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \> \>\> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7\> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Initial ABVD Treatment (2 Cycles) Withdrawal by Subject	0	9	0
Initial ABVD Treatment (2 Cycles) Ineligible	0	6	0

Baseline Characteristics

Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (ABVD x2 Cycles) n=164 Participants Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.\>\> * Doxorubicin 25 mg/m2 IV on Days 1 and 15\>\> * Bleomycin 10 units/m2 IV on Days 1 and 15\>\> * Vinblastine 6 mg/m2 IV on Days 1 and 15\>\> * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15\>\> \>\> PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD. \>\> \>\> Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP:\>\> Bleomycin 10 units/m2 IV on Day 8\>\> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \>\> Doxorubicin 35 mg/m2 IV on Day 1 \>\> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \>\> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \>\> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7\>\> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Age, Continuous	31 years n=5 Participants
Sex: Female, Male Female	76 Participants n=5 Participants
Sex: Female, Male Male	88 Participants n=5 Participants
Region of Enrollment United States	164 participants n=5 Participants

PRIMARY outcome

Timeframe: 36 Months

Population: All patients that received 4 cycles of ABVD were included in this analysis

Outcome measures

Outcome measures
Measure	Treatment (ABVD: 4 Cycles) n=135 Participants Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Escalated BEACOPP and Involved Field Radiation Therapy Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: \> \> Bleomycin 10 units/m2 IV on Day 8 \> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \> Doxorubicin 35 mg/m2 IV on Day 1 \> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 \> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD	.91 proportion of patients Interval 0.84 to 0.95	—

PRIMARY outcome

Timeframe: at 36 months

Population: All patients that completed an initial 2 cycles of ABVD were included in this endpoint.

All patients received an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15. After the first 2 cycles of ABVD, PET/CT was performed and submitted for central review (cycle 2, days 23-25) and determined whether patients would receive 2 cycles of escalated BEACOPP and involved-field RT (IFRT) or an additional 2 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS rate at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, we compare the PFS rate between patients who received 4 cycles of ABVD and patients who received 2 cycles of ABVD and 2 cycles of IFRT.

Outcome measures

Outcome measures
Measure	Treatment (ABVD: 4 Cycles) n=135 Participants Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Escalated BEACOPP and Involved Field Radiation Therapy n=14 Participants Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: \> \> Bleomycin 10 units/m2 IV on Day 8 \> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \> Doxorubicin 35 mg/m2 IV on Day 1 \> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 \> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
36 Month Progression Free Survival Rate of Patients Receiving 4 Cycles of ABVD Versus Patients Receiving 2 Cycles of ABVD and 2 Cycles of BEACOPP and Radiation.	.91 proportion of participants Interval 0.84 to 0.95	.67 proportion of participants Interval 0.34 to 0.86

SECONDARY outcome

Timeframe: Up to 5 years

Population: Two patients began a third cycle of ABVD and were not eligible for response evaluation (one withdrew and one was lost to follow up). Fourteen patients started BEACOPP treatment, and one patient was lost to follow-up and not included in this analysis.

A Complete Response (CR) was defined as having the following conditions: 1. A complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. In patients with a PET scan that was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET-negative. A Complete Response rate was defined as the number of patients who achieved a CR divided by the number of patients that were eligible for analysis in each group. The CR rate was calculated for patients that completed 4 cycles of ABVD and for patients that completed 2 cycles of ABVD and 2 cycles of BEACOPP and IFRT.

Outcome measures

Outcome measures
Measure	Treatment (ABVD: 4 Cycles) n=133 Participants Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Escalated BEACOPP and Involved Field Radiation Therapy n=13 Participants Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. * Doxorubicin 25 mg/m2 IV on Days 1 and 15 * Bleomycin 10 units/m2 IV on Days 1 and 15 * Vinblastine 6 mg/m2 IV on Days 1 and 15 * Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: \> \> Bleomycin 10 units/m2 IV on Day 8 \> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 \> Doxorubicin 35 mg/m2 IV on Day 1 \> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 \> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 \> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 \> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Complete Response Rate	.97 proportion of participants Interval 0.94 to 1.0	.85 proportion of participants Interval 0.65 to 1.0

Adverse Events

Only Initial Treatment (ABVD x2 Cycles)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Treatment (ABVD:4 Cycles)

Serious events: 12 serious events

Other events: 131 other events

Deaths: 0 deaths

Escalated BEACOPP and Involved Field Radiation Therapy

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

David J. Straus, MD

Alliance for Clinical Trials in Oncology

Phone: 212-639-8365

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Only Initial Treatment (ABVD x2 Cycles) n=15 participants at risk Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14	Treatment (ABVD:4 Cycles) n=135 participants at risk Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Escalated BEACOPP and Involved Field Radiation Therapy n=14 participants at risk Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: Bleomycin 10 units/m2 IV on Day 8 Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 Doxorubicin 35 mg/m2 IV on Day 1 Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Blood and lymphatic system disorders Anemia	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	3.7% 5/135 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Chest pain - cardiac	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Myocardial infarction	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Abdominal pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	3.0% 4/135 • Number of events 4 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Diarrhea	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Dyspepsia	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Mucositis oral	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Nausea	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	5.9% 8/135 • Number of events 8 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Vomiting	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
General disorders Chills	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
General disorders Fatigue	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	3.7% 5/135 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
General disorders Fever	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
General disorders Pain	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Infections and infestations Sepsis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Infections and infestations Skin infection	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Infections and infestations Soft tissue infection	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Alanine aminotransferase increased	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	2.2% 3/135 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Alkaline phosphatase increased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Aspartate aminotransferase increased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	2.2% 3/135 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations CD4 lymphocytes decreased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations CO diffusing capacity decreased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Ejection fraction decreased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Lymphocyte count increased	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Neutrophil count decreased	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	5.9% 8/135 • Number of events 8 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	14.3% 2/14 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations Platelet count decreased	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Investigations White blood cell decreased	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	5.2% 7/135 • Number of events 7 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	14.3% 2/14 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Anorexia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Dehydration	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hyperglycemia	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hypocalcemia	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Metabolism and nutrition disorders Hyponatremia	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Nervous system disorders Headache	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.

Other adverse events
Measure	Only Initial Treatment (ABVD x2 Cycles) n=15 participants at risk Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14	Treatment (ABVD:4 Cycles) n=135 participants at risk Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Escalated BEACOPP and Involved Field Radiation Therapy n=14 participants at risk Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: Bleomycin 10 units/m2 IV on Day 8 Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 Doxorubicin 35 mg/m2 IV on Day 1 Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Blood and lymphatic system disorders Anemia	13.3% 2/15 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	48.9% 66/135 • Number of events 169 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	50.0% 7/14 • Number of events 16 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	5.2% 7/135 • Number of events 7 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Blood and lymphatic system disorders Hemolysis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Chest pain - cardiac	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Palpitations	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Paroxysmal atrial tachycardia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Cardiac disorders Sinus tachycardia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	2.2% 3/135 • Number of events 4 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Ear and labyrinth disorders Ear pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	2.2% 3/135 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Ear and labyrinth disorders External ear pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Ear and labyrinth disorders Tinnitus	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Ear and labyrinth disorders Vertigo	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Eye disorders Blurred vision	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	3.0% 4/135 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Eye disorders Dry eye	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Eye disorders Eye disorders - Other, specify	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Eye disorders Eye pain	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Abdominal pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	8.1% 11/135 • Number of events 18 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Anal mucositis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Anal pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Bloating	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 4 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Constipation	26.7% 4/15 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	51.1% 69/135 • Number of events 134 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	35.7% 5/14 • Number of events 9 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Diarrhea	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	14.1% 19/135 • Number of events 28 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Dry mouth	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Dyspepsia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	12.6% 17/135 • Number of events 28 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	28.6% 4/14 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Dysphagia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Esophagitis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Flatulence	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 4 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gastric perforation	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gastritis	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	3.0% 4/135 • Number of events 5 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 2 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Gingival pain	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	7.1% 1/14 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.74% 1/135 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Hemorrhoids	6.7% 1/15 • Number of events 1 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/135 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Mucositis oral	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	21.5% 29/135 • Number of events 45 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	50.0% 7/14 • Number of events 11 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Nausea	26.7% 4/15 • Number of events 9 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	82.2% 111/135 • Number of events 288 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	71.4% 10/14 • Number of events 31 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Gastrointestinal disorders Oral dysesthesia	0.00% 0/15 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	1.5% 2/135 • Number of events 3 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.	0.00% 0/14 • Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.